Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators. This complexity can be demonstrated through field stimulation of isolated strips of corporal smooth muscle. Field stimulation of rabbit corpus cavernosum tissue strips can result in relaxation, contraction, or a biphasic response depending on the frequency and the power utilized. In our initial in-vitro studies we characterized the autonomic components of this response by exposing corporal tissue strips to a variety of autonomic agonists and antagonists including phentolamine, isoproterenol, methoxamine, propranolol, bethanechol, atropine and ATP. The results of these studies demonstrate that adrenergic, cholinergic, endothelial, and non-adrenergic, non-cholinergic [NANC] systems participate in the response of the corporal smooth muscle to field stimulation (either directly or indirectly). Many studies which utilize human corpus cavernosum obtain the tissue from transsexual males who have undergone castration and extended estrogen therapy. It is unclear what effects both castration +/- estrogen therapy has on the pharmacological response of the corpus cavernosum. This question is also of utmost importance for those men that begin this procedure but never complete the transsexual surgery. A second important clinical problem involves priapism (prolonged erection). This is especially prominent in the black community as it is associated with sickle cell anemia. The specific aim of this two year proposal is to 1) determine how castration +/- estrogen therapy alters the contractile and calcium translocation responses of the corpora to field stimulation, endothelial mediated relaxation, and pharmacological stimulated contraction and relaxation; and 2) develop the methodologies to investigate priapism in animal models. The long-term goals of these studies are to: 1) better define the autonomic mechanisms that regulate erection and detumescence, 2) Correlate these physiological functions with the cellular ionic processes that support the contractile / relaxation function of corporal smooth muscle, and 3) Determine how these physiological and ionic mechanisms are altered in specific experimental pathologies.