BJU international · 2006
alpha-Adrenoceptor subtypes in isolated corporal tissue from patients undergoing gender re-assignment.
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El-Gamal Osama M, Sandhu Davinder P S, Terry Tim, Elliott Ruth A
Аннотация
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.
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.