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Regulation of muscarinic acetylcholine receptors and contractility of guinea pig vas deferens

1981; Elsevier BV; Volume: 28; Issue: 5 Linguagem: Inglês

10.1016/0024-3205(81)90146-6

1879-0631

Kunio Takeyasu, Shuji Uchida, Rong‐Tsan Lai, Hiroshi Higuchi, Yutaka Noguchi, Hiroshi Yoshida,

Neuroscience and Neuropharmacology Research

The dynamic relationships between the muscarinic acetylcholine (m-ACh) receptor and the contractility of guinea pig vas deferens were studied by measuring the density of m-ACh receptors and contractile responses to ACh and high K+ (40 mM) under various experimental conditions. The guinea pig vas deferens has few spare muscarinic receptots for ACh. Brief treatment with dibenamine, an alkylating agent, decreases both the maximal contractile response to ACh and the number of m-ACh receptors to the same extent. The contractility of vas deferens, cultured for 3 days under a load of 320–1200 mg/muscle, was similar to that before culture. Addition of ACh to the culture medium resulted in a decrease in the sensitivity of the vas deferens to ACh and the number of muscarinic receptors in the muscle but did not affect noradrenaline-sensitivity, the amount of α-adrenergic (α-Ad) receptors or the high K+-stimulated contraction. The decrease in the number of muscarinic receptors was prevented by removing Ca2+ from the culture medium with EGTA. The smooth muscle relaxant, papaverine, partially antagonized the effect of ACh on the number of receptors. When muscles were transferred to normal medium after treatment with ACh, the amount of m-ACh receptors increased very slowly, and this increase was prevented by cycloheximide (5 mM). Colchicine, an anti-microtubule alkaloid, suppressed both the ACh-induced decrease in the receptor number and increase in the receptor numbers after its decrease. The following suggestions are proposed from these results: 1) The amount of m-ACh receptor determines the contractility of smooth muscle to ACh under physiological conditions. 2) Receptor activation, and/or resultant muscle activity by ACh can regulate the amount of m-ACh receptor, but not α-Ad receptor. 3) Microtubules seem to be involved in metabolic turnover of m-ACh receptor in smooth muscle.