An in vivo evaluation of alpha adrenergic receptors in canine prostate.
The role of alpha 2 adrenergic receptors in the prostate in vivo is unknown. A model was developed to measure canine prostatic urethral pressure in vivo, and to assess the ability of various alpha adrenergic blocking agents to affect prostatic pressure. In this model, an esophogeal pressure catheter is inserted into the prostatic urethra to record prostatic urethral pressure. We investigated the effects of alpha adrenergic agonists and antagonists on prostatic pressure using this model. Dose-response curves were generated for epinephrine, and were then repeated in the presence of either prazosin (alpha 1 antagonist), yohimbine (alpha 2 antagonist) or SK&F-86466 (alpha 2 antagonist). Prazosin was the most potent of the three drugs in competitively blocking epinephrine-induced contraction of the prostate, with an inhibition constant of 0.24 micrograms./kg. calculated from the double reciprocal plot. Clonidine, an alpha 2 adrenergic agonist, caused contraction of the prostate, which was also blocked by prazosin. Furthermore, the specific alpha 2 agonist BHT-920 was totally inactive in our system. These results demonstrate that the increase in urethral pressure caused by alpha-adrenergic agonists can be blocked by alpha adrenergic antagonists. However, the specific alpha 1 antagonist, prazosin, is more potent than alpha 2 antagonists, and is also effective against an alpha 2 agonist, clonidine. This suggests that blockade of alpha 1 receptors may be a more useful strategy for causing relaxation of the prostate than blockade of alpha 2 receptors.
Somers
W J
WJ
Department of Surgery/Division of Urology, James Buchanan Brady Foundation, New York, New York.
Felsen
D
D
Chou
T C
TC
Marion
D N
DN
Chernesky
C E
CE
Vaughan
E D
ED
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011312:Pressure; D011467:Prostate / Q000294:innervation*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D001552:Benzazepines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C024763:talipexole; D003000:Clonidine; D011224:Prazosin; C039139:benalfocin; D004837:Epinephrine