alpha-Adrenoceptor subtypes in isolated corporal tissue from patients undergoing gender re-assignment.

Abstract:

OBJECTIVE:To investigate the pharmacology and functionality of alpha(1)-adrenoceptors in human corpus cavernosum, and to determine the predominant subtype. MATERIALS AND METHODS:Cavernosal tissue specimens were obtained from the penises of 22 men (mean age 37.4 years) removed during gender re-assignment surgery. The men had been maintained on long-term oestrogen therapy before surgery, to aid the development of secondary feminine characteristics (oestrogen treatments were stopped 6 weeks before surgery). Corpus cavernosum strips were mounted in organ baths perfused with Krebs' solution. A control concentration-response curve (CRC) to phenylephrine (a nonselective alpha(1)-agonist) was obtained. Then the tissues were incubated with the alpha(1A) antagonist, WB4101; the alpha(1B) antagonist, chloroethylclonidine; or the alpha(1D) antagonist BMY 7378 (all at 1 microm) and the CRC to phenylephrine was repeated. The concentration producing a half-maximal response (EC(50)) and pK(B) values (logarithm of the dissociation constant, a measure of affinity) were determined. RESULTS:WB4101 produced a parallel rightward shift of the CRC to phenylephrine, with a pK(B) of 7.49. BMY 7378 also produced a parallel rightward shift of the CRC to phenylephrine with a pK(B) of 6.45. Chloroethylclonidine had a similar effect on the phenylephrine CRC, with a pK(B) of 5.90. CONCLUSION:Alpha(1)-adrenoceptors in human cavernosal tissue have a relatively low affinity for BMY 7378 and chloroethylclonidine, but are more sensitive to WB4101. This confirms that the predominant alpha(1)-adrenoceptor subtype in human corpus cavernosum is the alpha(1A) subtype and this might help in developing more selective antagonists and agonists for managing erectile dysfunction and priapism.

journal_name

BJU Int

journal_title

BJU international

authors

El-Gamal OM,Sandhu DP,Terry T,Elliott RA

doi

10.1111/j.1464-410X.2006.05956.x

keywords:

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

329-32

issue

2

eissn

1464-4096

issn

1464-410X

pii

BJU5956

journal_volume

97

pub_type

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