alpha-Adrenoceptor subtypes in isolated corporal tissue from patients undergoing gender re-assignment.
OBJECTIVE
To investigate the pharmacology and functionality of alpha(1)-adrenoceptors in human corpus cavernosum, and to determine the predominant subtype.


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.


CONCLUSIONS
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.
El-Gamal
Osama M
OM
Department of Urology, Tanta University, Tanta, Egypt. elgamalmd@yahoo.co.uk
Sandhu
Davinder P S
DP
Terry
Tim
T
Elliott
Ruth A
RA
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D058671:Adrenergic beta-1 Receptor Antagonists; D000328:Adult; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010413:Penis / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011317:Priapism / Q000188:drug therapy; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D014189:Transsexualism / Q000601:surgery
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D010656:Phenylephrine