Receptor-activated and energy-dependent decrease of muscarinic cholinergic receptors in guinea-pig vas deferens.

Organ cultures of guinea-pig vasa deferentia were used for studying both the decrease in muscarinic cholinergic receptor (mAChR) concentration induced by muscarinic agonists and the simultaneous decrease in contraction to ACh. After a lag period the decrease followed first-order kinetics and was completely blocked by atropine. The decrease was dependent not only on the extent of occupation of mAChR by ACh, but was also related to the efficacy of agonists as deduced from the contractions. Moreover the amount of mAChR was not affected by other contractile agents, norepinephrine and high K+ even under conditions in which mAChR was occupied by atropine or pilocarpine. These findings indicate that the decrease in the amount of mAChR mediated by muscarinic receptors in vas deferens was due to the extent of both receptor occupation and receptor activation by agonists. Furthermore it was shown that the decrease involved energy- and temperature-dependent processes and that cyclic nucleotides did not regulate the quantitative level of mAChR.