Impotence is a complication of several serious diseases, such as diabetes and atherosclerosis, as well as of therapeutic drug administration, and presents a profound psychological problem in this patient population. As yet, little is known about the physiology and biochemistry of the erectile process. We have demonstrated the uptake of (3H) choline, and the synthesis and release of (3H) acetylcholine (Ach) by nerves of human corpus cavernosum (CC). Cholinergic nerves appear to facilitate CC smooth muscle relaxation by modulation of other neuro effector systems. Ach induces relaxations of contracted strips and this effect requires the presence of endothelium. These observations suggest that acetylcholine and its muscarinic receptor (mAchR) may play a role in penile erection. To investigate the role of Ach and the muscarinic receptors in penile function it is essential to characterize by physico-chemical means the mAchR in CC. We plan to produce monoclonal and polyclonal anti-receptor antibodies and use them to investigate mAch receptor functions in CC. We will synthesize several oligopeptides with AA sequences representing various hydrophilic domains of M1 and M2 mAchR. Peptides will be coupled to Key Hole Limpet hemocyanin and used as antigens. The antibodies will be utilized to determine the concentration and distribution of mAchR in CC. Using immunochemical and immunohistochemical methods we plan to determine the density and localization of mAchR in the various cellular elements of human CC (e.g. smooth muscle, endothelial, and neural cells) and to see if differences exist in the density or distribution of mAchR in these various cellular elements. The data generated should be useful for future studies concerning the assessment of the effects of various systemic disease and pharmacological interventions on mAchR and its role in penile erections.
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