Effect of chronic morphine treatment on alpha(2)-adrenoceptor mediated autoinhibition of transmitter release from sympathetic varicosities of the mouse vas deferens.
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 When stimulating the sympathetic axons at 0.03 Hz, the mean EJP amplitude recorded from smooth muscles acutely withdrawn from CMT was four times greater than for CST smooth muscles (40.7+/-3.8 mV, n=7 compared with 9.9+/-0.3 mV, n=7). 4.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.
Karunanithi
S
S
Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
Lavidis
N A
NA
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*
D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D018377:Neurotransmitter Agents; D018341:Receptors, Adrenergic, alpha-2; D009020:Morphine; D003000:Clonidine