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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK040025-01
Application #
3240096
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-04-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Moreland, R B; Kim, N; Nehra, A et al. (2003) Functional prostaglandin E (EP) receptors in human penile corpus cavernosum. Int J Impot Res 15:362-8
Moreland, R B; Nehra, A; Kim, N N et al. (2002) Expression of functional prostaglandin D (DP) receptors in human corpus cavernosum smooth muscle. Int J Impot Res 14:446-52
Moreland, R B; Albadawi, H; Bratton, C et al. (2001) O2-dependent prostanoid synthesis activates functional PGE receptors on corpus cavernosum smooth muscle. Am J Physiol Heart Circ Physiol 281:H552-8
Udelson, D; L'Esperance, J; Morales, A M et al. (2000) The mechanics of corporal veno-occlusion in penile erection: a theory on the effect of stretch-associated luminal constrictability on outflow resistance. Int J Impot Res 12:315-27
Kim, N N; Goldstein, I; Moreland, R B et al. (2000) Alpha-adrenergic receptor blockade by phentolamine increases the efficacy of vasodilators in penile corpus cavernosum. Int J Impot Res 12 Suppl 1:S26-36
Traish, A; Kim, N N; Moreland, R B et al. (2000) Role of alpha adrenergic receptors in erectile function. Int J Impot Res 12 Suppl 1:S48-63
Moreland, R B; Kim, N N; Nehra, A et al. (2000) Misoprostol induces relaxation of human corpus cavernosum smooth muscle: comparison to prostaglandin E1. Int J Impot Res 12:107-10
Traish, A; Kim, N N; Huang, Y H et al. (2000) Cyclic AMP regulates mRNA expression of alpha-1d and alpha-2a adrenergic receptors in cultured human corpus cavernosum smooth muscle cells. Int J Impot Res 12 Suppl 1:S41-47
Traish, A M; Park, K; Dhir, V et al. (1999) Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 140:1861-8
Nehra, A; Gettman, M T; Nugent, M et al. (1999) Transforming growth factor-beta1 (TGF-beta1) is sufficient to induce fibrosis of rabbit corpus cavernosum in vivo. J Urol 162:910-5

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