Postjunctional supersensitivity of the smooth muscle of the rat vas deferens induced by calmodulin-antagonizing drugs applied locally to the hypogastric plexus.
Local application of 100 micrograms of chlorpromazine hydrochloride (CPZ) to the hypogastric plexus of the rat produced supersensitivity of the smooth muscle of the vas deferens. In comparison with surgical denervation, CPZ produced a similar increase in the maximum response but less leftward shift of the dose-response curves to norepinephrine. The changes in dose response curves to methacholine and potassium induced by CPZ were substantially similar to those induced by denervation. Virtually identical supersensitivity was brought about in the rat vas deferens by the same treatment with other drugs which possess calmodulin-antagonizing actions. CPZ produced no change in norepinephrine content of the tissue. Contractile responses of the tissue to tyramine were markedly potentiated by CPZ, but the responses to nerve stimulation were not significantly altered except for that at the lowest frequency. In electrophysiologic studies, while spontaneous junction potentials could be detected in all of the impaled cells, they occurred with lesser frequency and smaller amplitude in all of the impaled cells in the CPZ-treated rat vas deferens than in the control tissue. Nevertheless, the junction and action potentials could be induced by nerve stimulation in all smooth muscle cells. The results indicate that CPZ and also other drugs used in the present study produced postjunctional supersensitivity accompanied by a large increase in the maximum response, but almost no prejunctional supersensitivity in the rat vas deferens.
D000818:Animals; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002746:Chlorpromazine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007001:Hypogastric Plexus / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D002746:Chlorpromazine; D009638:Norepinephrine