title: Effect of chronic morphine treatment on alpha(2)-adrenoceptor mediated autoinhibition of transmitter release from sympathetic varicosities of the mouse vas deferens.
abstract: 1. The effect of chronic morphine treatment (CMT) on sympathetic innervation of the mouse vas deferens and on alpha(2)-adrenoceptor mediated autoinhibition has been examined using intracellular recording of excitatory junction potentials (EJPs) and histochemistry. 2. In chronically saline treated (CST) preparations, morphine (1 microM) and the alpha(2)-adrenoceptor agonist (clonidine, 1 microM) decreased the mean amplitude of EJPs evoked with 0.03 Hz stimulation by 81+/-8% (n=16) and 92+/-6% (n=7) respectively. In CMT preparations, morphine (1 microM) and clonidine (1 microM) decreased mean EJP amplitude by 68+/-8% (n=7) and 79+/-8% (n=7) respectively. 3. When stimulating the sympathetic axons at 0.03 Hz, the mean EJP amplitude recorded from smooth muscles acutely withdrawn from CMT was four times greater than for CST smooth muscles (40.7+/-3.8 mV, n=7 compared with 9.9+/-0.3 mV, n=7). 4. Part of the increase in mean EJP amplitude following CMT was produced by a 31% increase in the density of sympathetic axons and varicosities innervating the smooth muscle. 5. Results from the present study indicate that the effectiveness of alpha(2)-adrenoceptor mediated autoinhibition is only slightly reduced in CMT preparations. Most of the cross tolerance which develops between morphine, clonidine and alpha(2)-adrenoceptor mediated autoinhibition occurs as a consequence of increased efficacy of neuromuscular transmission which is produced by an increase in the probability of transmitter release and an increase in the density of sympathetic innervation.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Karunanithi
authors.forename: N A
authors.initials: NA
authors.lastname: Lavidis
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D018377:Neurotransmitter Agents; D018341:Receptors, Adrenergic, alpha-2; D009020:Morphine; D003000:Clonidine