Non-specific, time-dependent desensitization of the vas deferens and anococcygeus preparations of the rat to alpha 1-adrenoceptor antagonists and atropine.
Rat vas deferens preparations became desensitized to the alpha 1-adrenoceptor antagonist thymoxamine: after 6 h in vitro, the t 1/2 value (time to attain half the occupancy of receptors occupied at equilibrium) of the response to this drug was 1.50 fold greater in control strips (strips exposed to thymoxamine at 6 h) than in test strips (strips exposed to thymoxamine at 1 h). The rate of action of the alpha 1-adrenoceptor antagonist AR-C239 on the rat anococcygeus preparation was correlated with the rate of action of atropine. There was also a significant correlation between the t 1/2 ratios (1.37 and 1.30 for AR-C239 and atropine respectively) observed in the control muscles at 6 h. The in vitro slowing is thus due to some change in the longitudinal muscle and not to a change in the receptors. The in vitro slowing occurred when either phenylephrine or methoxamine was the alpha 1-adrenoceptor agonist used. The most likely mechanism of desensitization is a non-specific slowing of the access of drugs to receptors.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D013948:Moxisylyte / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D001285:Atropine; D002217:Carbachol; D013948:Moxisylyte