characterization of intestinal smooth muscle responses and binding sites for endothelin the contractile activity of and binding sites for endothelin1 et1 were investigated in isolated guineapig ileal longitudinal smooth muscle gpilm et1 produced concentrationdependent contractions of gpilm that either slowly subsided in the continued presence of et1 or rapidly subsided following washing of the tissue the ed50 value for et1 contractions was 42 13 x 109 m the removal of extracellular calcium or pretreatment with nifedipine produced a complete inhibition of the contractions to et1 the ic50 value of nifedipine for inhibition of et1 mediated contractions was 30 08 x 108 m et1 produced a marked prolonged homologous desensitization of its contractile response but did not affect the responses mediated by carbachol histamine serotonin substance p and pla2 highaffinity binding sites for 125ilabelled et1 were identified on microsomal membranes prepared from gpilm with kd and bmax values obtained by scatchard analysis of 35 06 x 1010 m and 2138 159 fmolmg protein respectively the binding of 125ilabelled et1 to gpilm microsomes was characterized by a rapid association kob value of 0077 min1 at a radioligand concentration of 045 nm and an extremely slow dissociation k1 value of 0011 min1 t12 value of 793 min the binding was unaffected by the calcium channel antagonists nifedipine verapamil and diltiazem 106 m the receptor antagonists phenoxybenzamine atropine and naloxone 106 m and propranolol and the peripheral benzodiazepine receptor antagonists ro 54864 and pk 11195 and psychotomimetic drug phencyclidine 105 mabstract truncated at 250 words