EFFECTS OF DENERVATION, COCAINE, 6-HYDROXYDOPAMINE AND RESERPINE ON CHARACTERISTICS OF DRUG-INDUCED CONTRACTIONS OF DEPOLARIZED SMOOTH-MUSCLE OF RAT AND GUINEA-PIG VAS-DEFERENS

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 201  (2) , 267-275
Abstract
Postjunctional supersensitivity of the vas deferens was previously suggested to be due in part to altered electrophysiological properties, the sensitivity of the muscle being increased to any agonist which initiates contraction by means of depolarizing the cell membrane. Altered electrical properties are probably not the only postjunctional changes which can account for the enhanced response. Dose-response curves for stimulant agonists were obtained in isolated vasa deferentia which were depolarized by a K-rich, Na-free solution. Chronic denervation resulted in a 2- to 3-fold displacement of the dose-response curve for norepinephrine to the left of control. Cocaine (10-5 M) did not potentiate the response to norepinephrine of the innervated, depolarized smooth muscle. Supporting the contention that the supersensitivity of the depolarized tissue is postjunctional in nature was the finding that the denervated vas deferens was supersensitive to methoxamine, an agent which is not taken up by the neuronal amine transport system. Pretreatment of rats with reserpine (1.0 mg/kg per day for 5-7 days) also produced supersensitivity of the depolarized vas deferens. The increased maximal response to drugs of the denervated rat vas deferens which is observed in normally polarized tissues is absent in depolarized tissues, suggesting that the phenomenon of increased maximum requires the existence of a membrane potential in order to be manifest. The denervated vas deferens, but not the vas deferens from reserpine-pretreated animals, exhibits an increase in the duration of drug-induced contractions. This effect occurs in normal and depolarizing salt solutions, suggesting that the change which leads to this phenomenon differs from those alterations which lead to postjunctional supersensitivity and to the enhanced maximal response.