Functional characterization of alpha-1-adrenoceptor subtypes in the prostatic urethra and trigone of male rabbit.
The effects of alpha-1-adrenoceptor antagonists on the concentration-response curves (CRC) to phenylephrine and oxymetazoline have been studied in prostatic urethra and trigone of male adult rabbits (28 wk old). WB4101 and phentolamine, at low concentrations which should preferentially antagonize the alpha-1A-adrenoceptor subtype, did not modify the oxymetazoline-induced contraction of both prostatic urethra and trigone, suggesting that alpha-1A-adrenoceptors are not activated under these conditions. In urethra, pretreatment with 50 microM chloroethylclonidine (CEC), significantly reduced the maximal contraction to both agonists to 60 and 70% of control, respectively. In trigone, CEC decreased the maximum contraction to phenylephrine, but not to oxymetazoline, by 50%. In addition, CEC shifted to the right the CRC to both agonists. These results suggest the presence of an alpha-1B-adrenoceptor in both rabbit urethra and trigone. Exposure to prazosin (0.01-1 microM) significantly shifted to the right the CRC to phenylephrine (pA2 or affinity values without CEC treatment: 7.77 and 7.96 in urethra and trigone respectively; with CEC pretreatment: 7.49 and 7.42, respectively). When oxymetazoline was used as an agonist and in the presence of CEC, prazosin was unexpectedly weak in urethra with an affinity value of 6.70, although the antagonist potency was not modified in trigone (affinity 7.38). These values suggest that alpha-1-adrenoceptor agonists contract rabbit urethra and trigone through activation of alpha-1-adrenoceptors displaying low affinity for prazosin. Whether this receptor coincides with the alpha-1L- or alpha-1N-subtype remains to be clarified.
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Synthélabo Recherche (L.E.R.S.), Cardiovascular Department, Bagneux, France.
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D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects*; D011817:Rabbits; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D014521:Urethra / Q000187:drug effects*
D000322:Adrenergic Agonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D010109:Oxymetazoline; D009638:Norepinephrine