agent which triggers anion efflux in respiratory tissue via the activation of a secretin receptor . there are a number of mechanisms by which secretin receptors may be activated . for example , expression of secretin is widely reported to be restricted to s - type enteroendocrine cells in the small intestine and colonic enteroendocrine cells and insulin producing β cells of the developing pancreas . both enteroendocrine cells and pancreatic islets arise from the primitive embryonic gut endoderm . in addition , the primary airways are formed through a process termed branching morphogenesis , whereby two ventral lung buds sprout from the epithelium lining the floor of the embryonic foregut endoderm . patterning of the airways is then accomplished by the outgrowth and repetitive branching of the two long buds . pulmonary neuroendocrine ( pne ) cells are amongst the first cells to differentiate from the primitive lung epithelium , and are generally most abundant in the airways of fetal and neonatal lungs . these cells are known to express a number of peptides including calcitonin , calcitonin gene related peptide , serotonin and endothelin , and can be visualized by their immunoreactivity to these peptides or to general endocrine markers such synaptophysin , chromogranin and protein gene product 9 . 5 . in the cf bronchus , increased calcitonin immunoreactivity within endocrine cells has been demonstrated ( wolf et al , 1986 ). further , the secretin gene may be upregulated by the provision of agents which increase the level of transcription of the gene , e . g . via promoter or enhancer regulation . the enhancer region of the secretin gene contains a cis - acting dna consensus sequence ( cagctg ) known as an e box , which bind proteins belonging to the basic helix - loop - helix ( bhlh ) family of transcription factors . a bhlh protein known as beta2 / neurod has been demonstrated to lead to the tissue - specific regulation of secretin gene transcription ( mutoh et al , 1997 ). in knock out mice , beta2 / neurod deficient mice fail to develop enteroendocrine cells or pancreatic β cells , demonstrating the critical role of this transcription factor in the normal development of several specialized cells types that arise from the gut endoderm . beta2 / neurod expression has been demonstrated to locate only to endocrine cells in transgenic mice ( rhindi et al , 1999 ). in addition , up regulation of endogenous secretin production may also be achieved by a variety of other methods known in the art ( e . g . see jiang et al ., 2001 ; yang et al ., 1998 ; morse et al ., 2001 ; lewis et al ., 1997 ; west & amp ; rodman , 2001 ; alton & amp ; kitson , 2000 ) including but not limited to gene therapy ( delivery of dna or rna in a viral or non viral vector encoding a peptide capable of directly or indirectly stimulating the secretin receptor or its cell signalling pathway ), or gene targeting ( delivery of agents which target regulatory sequences or transcription factor binding sites on the promoter region of the gene encoding secretin or a related peptide , thereby switching on production of secretin or a related peptide capable of directly or indirectly stimulating the secretin receptor ). a number of mechanisms are known to stimulate secretin release , including the following : agents such as dibutyryl cyclic - 3 ′, 5 ′- adenosine monophosphate , forskolin , 4 beta - 12 - o - tetradecanoylphorbol - 13 - acetate , the synthetic serine protease inhibitor , camostat , and the calcium ionophore , a2318 , which stimulate ca 2 + and cyclic - 3 ′, 5 ′- adenosine monophosphate - dependent secretin release ( xue et al , 1993 ); pancreatic phospholipase a 2 ( pla 2 ) which has been demonstrated to intrinsically possess secretin - releasing activity , which is independent of its digestive enzymatic activity ( chang et al , 1999 ); the neuropeptides bombesin , gastrin releasing peptide , vip and galanin have also been shown to modulate secretin release in secretin - producing cells ( chang et al , 1998 ); and long chain fatty acids , such as sodium oleate are potent stimulators of secretin release from endocrine cells . their stimulatory effect is potentiated by endogenous protein kinase a and mediated by activation of ca 2 + influx through the l - type channels and of protein kinase c and ca 2 + / calmodulin - dependent protein kinase ii ( chang et al , 2000 ). further , receptor activity modifying proteins , or ramp are novel single transmembrane domain proteins that can modulate the expression and / or activity of at least two members of the secretin receptor gpcr family . to date there are 3 ramp isoforms , 1 - 3 , whose interactions are suggested to potentially result in trafficking of the receptor to the cell surface , modifying the degree of receptor glycosylation , and / or contributing to the ligand binding site through association with the receptor at the cell surface ( sexton , 1999 ). ramps may indirectly alter a peptide selectivity for a specific receptor of the secretin gpcr family . for example , studies in which a single point mutation of the pth1 receptor confers secretin responsiveness to this receptor , while the reverse mutation confers pth responsiveness to the secretin receptor ( turner et al , 1996 ) has been suggested could be due to alterations in specific ramp interactions with the receptor . ( sexton , 1999 ). as such , agonism of the secretin receptor could be mediated via the simultaneous or sequential application of a peptide analogue or fragment of the secretin receptor family and a specific ramp . respiratory tissue in which secretin receptors are activated particularly includes tissue within the distal regions of the lung selected from tertiary bronchus and lung parenchyma . as indicated above , the preferred secretin receptor ligand is human secretin ( hsn ). however other mammalian secreting , such as the closely related bovine , porcine or pig secretin , or canine , rodent , chicken and rabbit secretin ( which exhibit various degrees of homology to human secretin ), may be used , as well other naturally occurring or synthetic fragments or analogues of secretin , such as those identified herein . various other secretin receptor ligands are well known in the art . many such ligands are based on the sequence of a natural secretin ( e . g . human or porcine secretin ) but contain from 1 to 7 ( more usually from 1 to 5 , and often 1 , 2 or 3 ) amino acid substitutions or deletions , particularly but not exclusively in the n - terminal region . for example , gespach et al ( 1986 ) describe four synthetic secretin analogues including one corresponding to porcine secretin substituted at the n - terminus by sequence portions of vasoactive intestinal peptide ( vip ), i . e . ala4 - val5 - psn , together with tyr1 - ala2 - glu3 - psn , gln3 - psn , phe1 - phe2 - trp3 - lys4 - psn . konig et al ( 1977 ) describe ala4 - psn . gardener et al ( 1976 ) describe the secretin fragment sn5 - 27 and three variants thereof , ( 9gln - sn5 - 27 , 15asn - sn5 - 27 and 9gln - 15asn - sn5 - 27 ). 15 - lys - sn has also been described in the art ( gardener et al , 1979 ). haffer et al ( 1991 ) describe eight secretin variants with reduced peptide bonds ( the — conh — bond being replaced by — ch2 — hn —) between one of the eight n - terminal peptide bonds . robberecht et al ( 1988 ) describe secretin fragments 2 - 27 , 3 - 27 , 5 - 27 and 7 - 27 and observed activity for secreting receptors . konig et al ( 1986 ) exchanged the n - terminal 5 amino acids of a secretin for the n - terminal pentapeptide sequence of human somatotropin releasing factor to provide 1 - tyr - 2 , 4 - diala - 5 - ile - sn , which showed secretin activity . other active variants made were 3 - l - cystic acid - sn , 6 - d - phe - sn , 5 - allo - thr - sn , and 1 - cys - 6 - cys - sn . further examples of secretin analogues which exhibit affinity for the secretin receptor include , [ ala4 , val5 ] and [ d - ala4 , val5 ] secretin , ( d - ala4 ) secretin ; ( d - phe6 ) secretin ; secretin 5 - 27 , secretin 14 - 27 [ val5 ] secretin , [ d - ala4 , val5 ] secretin ( waelbroeck et al , 1981 ); substituted fragments such as [ gln9 , asn15 ] secretin ( 5 - 27 ) ( staun - olsen et al , 1986 ); phenolic group containing analogues of porcine secretin including nalpha - tyrosylsecretin , [ tyr1 ] secretin , and nalpha - beta -( 4 - hydroxyphenyl ) propionylsecretin ( yanaihara et al , 1977 ); carboxyl - terminal tricosapeptide analogues of secretin ( s5 - 27 ) ( 9 - gln - s5 - 27 , 15 - asn - s5 - 27 ), and 9 - gln - 15 - asn - s5 - 27 ) ( gardner et al , 1976 ). vasoactive intestinal peptide ( vip ), pacap , glucagon , glucagon - like peptide and naturally occurring and synthetic analogues and fragments thereof , exhibit considerable homology to that of secretin . examples of these include but are not limited , to ( d - ala4 ) vip ; ( d - phe4 ) vip ; ( d - phe2 ) vip , fatty acyl derivatives of vip , including myristyl -, palmityl - and stearyl -[ nle17 ] vip ( gourlet et al , 1998 ), vip 2 - 28 ; vip 1 - 14 ; vip 2 - 14 ; vip 14 - 28 ; vip 15 - 28 ; vip 20 - 28 ; vip 21 - 28 , two sequences where the n - terminal vip 1 - 6 or vip 1 - 9 have been joined covalently with the c - terminal vip 20 - 28 or vip 21 - 28 ( couvineau et al , 1984 ); vip 7 - 27 , vip 11 - 28 , vip 1 - 22 - nh 2 , vip 16 - 28 ( staun - olsen et al , 1986 ), vip [ 10 - 28 ] and vip [ 16 - 28 ]. analogues of secretin and vip , referred to as the vasectrins , have also been described by beyerman et al , 1981 . pacap ( 1 - 27 ; 1 - 38 ) and analogue examples include pacap ( 1 - 23 , vip - 24 - 28 ), pacap ( 1 - 24 , cys - 25 ), pacap ( 1 - 23 ), pacap ( 3 - 27 ), pacap ( 1 - 19 ), pacap ( 3 - 19 ), pacap ( 1 - 12 ), and pacap ( 18 - 38 ) ( schmidt et al , 1993 ), glucagon , and glp - 1 , and their related analogues and fragments include glp - 1 ( 7 - 37 ) glp - 1 -( 1 - 37 ) amide , -( 6 - 37 ) amide , -( 8 - 37 ) amide , -( 7 - 36 ) amide ( suzuki et al , 1989 ), those with alterations in the n - terminal position 1 including n - methylated - ( n - me - glp - 1 ), alpha - methylated ( alpha - me - glp - 1 ), desamidated - ( desamino - glp - 1 ) and imidazole - lactic - acid substituted glp - 1 ( imi - glp - 1 ). ( gallwitz et al , 2000 ). the secretin receptor ligands described in the above literature , which is incorporated herein by reference , may all be used in the present invention , though those of skill in the art will appreciate that the above - cited references are not exhaustive and other secretin receptor ligands may be used . the suitability of candidate ligands may be determined experimentally . for example , charlton et al ( 1983 ) report that secretin injected intracerebroventricularly significantly increased defecation and decreased novel - object approaches in rats , but showed no significant effects on stereotypic behaviour . such a test may be performed in rats with a secretin receptor ligand to determine its suitability for the present invention ( i . e . those ligands which show similar effects via agonism of the secretin receptor may be selected ). secretin is available from commercial sources ( e . g . peninsula laboratories inc , usa ) or it and the above - described ligands may be obtained by reference to readily available published literature . the novel findings reported herein give rise to novel compositions which comprise a secretin receptor ligand together with at least one other compound active against asthma , generally agents which produce airway relaxation or enhance mucus clearance . such compounds include but are not limited to beta - agonist ( e . g . salbutamol , salmeterol ), disodium cromoglycate , steroids and inhibitors of pde iv . the amount of secretin receptor ligand in such a composition may be , for example , from 1 % to 99 % by weight of the total amount of active ingredients ( i . e . excluding carriers or diluents ), for example from 10 % to 90 % by weight . in a related aspect , the present invention provides a combination of a secretin receptor ligand and a second compound active against asthma for simultaneous or sequential use in the treatment of asthma . by “ simultaneous ” it is meant that the two compounds are administered at the same time , though not necessarily in the same composition . by “ sequential ” it is meant that the two compounds are administered within a time period such that the first of the two compounds is still active in the patient when administration of the second of the two compounds occurs . preferably , “ sequential ” means within the same 24 hour , preferably within the same 12 hour , such as within the same 6 , 3 , 1 , half or quarter hour time period . treatment of patients in accordance with the present invention may be performed by administering to a patient a secretin receptor ligand in the form of a pharmaceutical composition , either with or without a further active ingredient present ( reference below to compositions will be understood to include both types , though for brevity only the secretin receptor ligand is specifically mentioned ). the composition may be in combination with a non - toxic , pharmaceutically acceptable carrier . in this context the invention also covers a method of treating asthma comprising administering a therapeutically effective amount of the secretin receptor ligand of this invention or a composition of this invention on a patient to be treated . in clinical practice the compositions of the present invention may be administered parenterally due to the fact that being a peptide the hormone is sensitive to biologically active environments . oral or rectal administration may , however , be conceivable , for example using compositions of the slow release type making it possible for the active ingredient to reach the site of primary interest , namely the tertiary bronchus . secretin receptor ligands may be formulated in a suitable form for administration by inhalation ( e . g . via an aerosol ) or insufflation ( either through the mouth or nose ), or by parenteral administration ( introduced by routes other than intestinal routes ). delivery of proteins or peptides via inhalation may be accomplished using liquid or solid preparations of the secretin receptor ligand . thus the invention contemplates formulations comprising secretin receptor ligand for us in a wide variety of devices that are designed for the delivery of pharmaceutical compositions and therapeutic formulations to the respiratory tract . in one aspect of the present invention , secretin receptor ligand is administered in aerosolized or inhaled form . the secretin receptor ligand , combined with a dispersing agent , or dispersant , can be administered in an aerosol formulation as a dry powder or in a solution or suspension with a diluent . suitable dispersing agents are well known in the art , and include but are not limited to surfactants and the like . surfactants are generally used in the art to reduce surface induced aggregation of protein caused by atomization of the solution forming the liquid aerosol . examples of such surfactants include polyoxyethylene fatty acid esters and alcohols , and polyoxyethylene sorbitan fatty acid esters . amounts of surfactants used will vary , being generally within the range of about 0 . 001 to 4 % by weight of the formulation . in a specific aspect , the surfactant is polyoxyethylene sorbitan monooleate or sorbitan trioleate . the liquid aerosol formulations contain the secretin receptor ligand and a dispersing agent in a physiologically acceptable diluent . the dry powder aerosol formulations of the present invention consist of a finely divided solid form of the secretin receptor ligand and a dispersing agent , and optionally a bulking agent , such as lactose , sorbitol , sucrose , or mannitol , and the like , to facilitate dispersal of the powder . with either the liquid or dry powder aerosol formulation , the formulation must be aerosolized . that is , it must be broken down into liquid or solid particles in order to ensure that the aerosolized dose actually reaches the bronchi and / or alveoli , as desired . in general the mass median dynamic diameter will be 5 micrometers ( μm ) or less in order to ensure that the drug particles reach the lung bronchi or alveoli ( wearley et al 1991 ). with regard to construction of the delivery device , any form of aerosolization known in the art , including but not limited to nebulization , atomization or pump aerosolization of a liquid formulation , and aerosolization of a dry powder formulation , can be used in the practice of the invention . a delivery device that is uniquely designed for administration of solid formulations is envisioned . often , the aerosolization of a liquid or a dry powder formulation will require a propellant . the propellant can be any propellant generally used in the art . examples of useful propellants include chlorofluorocarbons , hydrofluorocarbons , hydrochlorofluorocarbons , and hydrocarbons , including trifluoromethane , dichlorodifluoromethane , dichlorotetrafluoroethanol , and 1 , 1 , 1 , 2 - tetrafluoroethane , and combinations thereof . in a preferred aspect of the invention , the device for aerosolization is a metered dose inhaler . a metered dose inhaler provides a specific dosage when administered , rather than a variable dose depending on administration . such a metered dose inhaler can be used with either a liquid or a dry powder aerosol formulation . systems of aerosol delivery , such as the pressurized metered dose inhaler and the dry powder inhaler are disclosed in newman , aerosols and the lung , clarke , s . w . and davia , d . editors , pp 197 - 22 and can be used in connection with the present invention . additional pharmaceutical methods may be employed to control the duration of action of the antagonists of this invention . the antagonists also may be entrapped in microcapsules prepared , for example , by coacervation techniques by interfacial polymerisation ( for example , hydroxymethylcellulose or gelatin - microcapsules and poly -( methylmethacrylate ) microcapsules , respectively ), in colloidal drug delivery systems ( for example , liposomes , albumin microspheres , microemulsions , nano - particles and nanocapsules ), or in macroemulsions . such techniques are disclosed in remington &# 39 ; s pharmaceutical sciences , 16th edition , osol , a ., ed ( 1980 ). for intranasal administration , the secretin receptor ligands may be formulated as solutions for administration via a suitable metered or unit device or alternatively as a powder mix with a suitable carrier for the administration using a suitable delivery device . alternatively , secretin receptor ligands could be delivered transnasally in a similar fashion . for example , preparation of secretin for transnasal administration has been described in jp60123426 . preparations for parenteral administration includes sterile aqueous or non - aqueous solutions , suspensions or emulsions . examples of non - aqueous solvents or suspending media are propylene glycol , vegetable oils , such as olive oil , and injectible organic esters , such as ethyl oleate . these compositions may also contain adjuvants , such as preserving , wetting , emulsifying and dispersing agents . they may be sterilized , for example , by filtration through a bacteria - retaining filter , by incorporation of sterilizing agents in the composition , by irradiation or by heating . they may be also be manufactured in the form of sterile solid compositions , which can be dissolved in a sterile injectible medium immediately before use . as well as the more customary intravenous and intramuscular routes the compositions may also be administered by intraarticular injection . the percentages of active ingredient in the compositions of the invention may be varied as long as they constitute a proportion such that a suitable dosage for the desired stimulatory effect on the pancreas is obtained . obviously several unit dosage forms may be administered at about the same time . generally , the compositions should contain from about 0 . 1 % to about 80 % by weight of active ingredient . the dose employed depends upon the desired stimulatory effect , the route of administration and the duration of the treatment . typical doses may be in the range of from 10 − 8 to 10 − 3 mg per day , preferably from 10 − 6 to 10 − 4 mg per day for a human patient . the secretin receptor ligand may be administered each day or , according to the wishes of the medical practitioner , less often , e . g . weekly , or until the desired therapeutic effect is achieved . messenger rna expression profiles of the secretin receptor ( protein accession p47872 ; nucleotide accession u28281 ) was examined . total rna was isolated from tertiary / quaternary bronchus and lung parenchyma from 5 control and 5 asthma donors using trizol ™ a commercially available solution of phenol and guanidine isothiocyanate , according to the protocol described by the manufacturer ( life technologies ). samples of rna were used only if intact 18s and 28s ribosomal rna were detected by gel electrophoresis and if genomic dna formed less than 10 % of the total nucleic acid sample . total rna samples were annealed to the primer probe sequence plus a glyceraldehyde - 3 - phosphate dehydrogenase ( gapdh ; accession no . p04406 ) primer and reverse transcribed using mulv reverse transcriptase . quantitative sequence detection was carried out on the resulting cdna . the applicants have developed protocols for quantitative analysis of mrna expression using the abi prism 7700 sequence detection system ( perkin elmer ). details of the system are set out in wo00 / 05409 . in brief , the system uses fluorogenic probes to generate sequence specific fluorescent signals during pcr . the probes are oligonucleotides with fluorescent reporter and quencher dyes attached . while a probe is intact , the intensity of reporter fluorescence is suppressed by a quencher . when a probe forms part of a replication complex during the pcr process , the quencher is separated from the reporter dye resulting in a increase in fluorescence which is then detected by the abi 7700 sequence detector . the abi 7700 has a built in thermal cycler , and a laser directed at each of the 96 sample wells via bi - directional fibre optic cables . emitted fluorescence through the cables to a detector where emissions which fall between 520 nm and 660 nm are collected every few seconds . the system software analyses the contribution of each component dye to the experiment spectrum , and normalises the signal to an internal reference dye . the peaks of these normalised ‘ reporter ’ values ( rn ) are then plotted against thermal cycle number to produce an amplification plot — to allow visualisation of the extent of pcr product generation . the starting copy number of a target sequence ( cn ) is established by determining the - fractional pcr cycle number ( ct ) at which a pcr product is first detected — the point at which the fluorescence signal exceeds a threshold baseline . therefore the lower a ct value the greater the cn . quantification of the amount of target mrna in each sample is established through comparison of the - experimental ct values with standard curves for the target sequence which are constructed during each experiment . primer probe sets were specifically designed for the detection of secretin receptor mrna . off - line homology searches revealed no significant matches with gene sequences logged at genbank . forward and reverse primer and probe sequences for the secretin receptor were as follows : forward gaccagcatcatctgagaggct ( seq id no : 1 ) reverse ccttcgcaggacctctcttg ( seq id no : 2 ) probe tctctgtccgtgggtgaccctgct ( seq id no : 3 ) forward gaaggtgaaggtcggagtcaac ( seq id no : 4 ) reverse cagagttaaaagcagccctggt ( seq id no : 5 ) probe tttggtcgtattgggcgcct ( seq id no : 6 ) reaction conditions were optimised using genomic dna as a template and a primer probe concentration grid followed by a probe concentration gradient experiment . primer concentrations were selected to give the most efficient amplification of gene product , i . e . those which generate a low threshold cycle and a relatively high accumulation of fluorescence . these optimal primer concentrations were then used to select the optimum probe concentration the data from 5 patients with asthma and 5 normal controls are shown in fig2 . data are expressed as mean ± s . e . mean of the target threshold cycle ( tct ), whereby a lower threshold cycle represents an increased mrna abundance . functional activity of the secretin receptor was examined in the tertiary bronchus and in epithelial cells derived from the tertiary bronchus of normal tissue . in brief , non - branching regions of the human tertiary bronchus from non - asthma donors were dissected , cut longitudinally and mounted in between the two compartments of a modified ussing chamber to measure the short circuit current across the bronchial wall . both luminal ( airway ) and basolateral membranes were bathed in oxygenated krebs extracellular solution and the tissue voltage clamped to zero to allow changes in short circuit current in response to secretin to be measured . amiloride at a concentration of 10 μm was initially added to the luminal membrane ( fig3 point a ) ( as described by those in the art ) to partially block the predominant sodium ion current and unmask underlying ionic currents . on attainment of a stable base line , 3 μm human secretin ( supplied by sigma , catalogue number s714 ) was added to the luminal membrane ( fig3 point b ). secretin was found to stimulate ionic movement in a manner consistent with the movement of a negatively charged ion ( cl − and / or hco 3 − ( fig3 ). like secretin , addition of 10 μm atp or utp to the apical membrane of the lung epithelium ( fig3 point c ) was demonstrated to stimulate a similar ionic movement of similar magnitude . these atp and utp mediated effects are widely reported in the literature to be due to the stimulation of a ca 2 + - activated cl − current via the p2y2 purinoceptor . both described agonists , at high concentrations produced responses of a similar magnitude . functional effects of the secretin receptor were probed in epithelial cells derived from the human tertiary bronchus . in brief , tertiary bronchial epithelial were isolated by overnight protease digestion and then cultured until confluency on snapwell ( costar ) permeable supports . the supports were mounted in a modified ussing chamber , and both luminal and basolateral membranes were bathed in oxygenated krebs extracellular solution . the cells were voltage clamped to zero to allow changes in short circuit current in response to secretin to be measured . as previously described , 10 μm amiloride was initially added to the luminal membrane ( fig4 point a ) followed by the addition of 100 nm secretin to the luminal membrane ( fig4 point b ). consistent with observations in the tertiary bronchus , secretin stimulated ionic movement in a manner consistent with the movement of a negatively charged ion ( cl − and / or hco 3 − ). furthermore , addition of 500 μm glibenclamide ( point c ), a recognised inhibitor of the cftr failed to suppress secretin mediated ionic movement , suggestive that a similar ionic movement would be observed in cf tertiary bronchial epithellal cells . ionic movement in tertiary bronchial epithelial cells was further characterised with the use of the cl − specific fluorescent probe mqae ( n -( ethoxycarbonylmethyl )- 6 - methoxyquinolinium bromide ; molecular probes ). in brief , primary human , tertiary bronchial epithelial cells were isolated as described above and cultured in a 96 well plate . on reaching confluency , cells were loaded overnight with 4 mm mqae . cells were washed in a chloride containing hepes buffer , before passive cl − efflux was initiated by the addition of a cl − free buffer . addition of 12 . 5 nm or 100 nm concentrations of secretin stimulated cl − efflux , as determined by changes in mqae fluorescence . the results are shown in fig5 a ( open diamonds 12 . 5 nm ; closed circles 100 nm secretin ). the 100 nm secretin mediated changes in fluorescence were abolished by the addition of 100 μm of the - non - selective cl − channel blocker nppb ( 5 - nitro - 2 -( 3 - phenylpropyl - amino ) benzoic acid ( open circles ) . unstimulated cl − efflux is demonstrated by the closed squares . the experiment of example 3a above was repeated using a range of secretin concentrations from 1 to 1000 nm . representative data from a single experiment from 6 independent experiments are shown in fig5 b . maximal secretin stimulated cl − efflux was of a similar magnitude to that observed to prostaglandin e 2 ( 10 μm ). secretin concentration - dependently stimulated cl − efflux with nanomolar affinity ( log ec 50 ( m )- 7 . 64 ± 0 . 24 ; 22 . 9 nm — see fig6 ). responses at each concentration were normalised to those observed to pge 2 ( fig5 a open circles , 10 μm ) and are representative of the mean ± s . e . mean from 2 to 6 independent experiments on cells derived from 6 donors ). the bronchorelaxant properties of secretin was examined in vitro , in the tertiary bronchus of non - diseased tissue . in brief , tertiary bronchial rings ( 1 - 3 mm internal diameter ) were mounted in 10 ml organ baths under a resting tension of 10 mn ( 1 g ) and bathed with oxygenated krebs &# 39 ; solution at 37 ° c . tissues were precontracted with carbachol at the concentration being that which caused a contraction approximately 60 - 70 % of the maximum , and a cumulative concentration - effect contractile curve ( cec ) to secretin ( 0 . 01 μm to 3 μm ) was constructed on each preparation . isoprenaline ( 1 μm ) was subsequently administered to demonstrate maximal relaxatory responses . secretin ( 0 . 01 μm to 3 μm ) caused concentration - 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the invention is based on the finding that the secretin receptor is expressed in tissues present in the distal lung of humans . in patient with asthma , levels of the receptor are elevated compared to normal tissue . treatment of tissue by secretin stimulates the movement of negative ions in the tissue . addition of secretin to human bronchial tissue in vitro stimulates bronchorelaxation . the invention provides methods of treatment of asthma in a patient by administering to said patient an effective amount of an agent which triggers anion efflux and bronchorelaxation in respiratory tissue via the activation of a secretin receptor .