Calcium reverses the inhibitory action of morphine on neuroeffector transmission in the mouse vas deferens.
In the mouse vas deferens, the amplitude of excitatory junction potentials (e.j.p.s.) recorded intracellularly from smooth muscle cells was found to be proportional to stimulus intensity. Normorphine (0.4-2-10 microM) reduced the amplitude of these postsynaptic transients and shifted the stimulus-response curve to the right; i.e. in its presence, higher stimulus intensities were required to elicit an e.j.p. of a similar size to one generated in its absence. Naloxone (0.4 microM) reversed the inhibitory effect of normophine (2 microM). Membrane potentials were unaffected by the concentrations of normorphine employed in solutions of varying ionic compositions. Manoeuvres designed to increase intracellular free calcium, that is increasing the extracellular Ca+ ion concentration (from 2.5 to 5 or 10 mM), removing Mg2+ ions from a medium containing 5 mM Ca2+ or applying 4-aminopyridine (100 microM), enhanced the e.j.p. amplitude and reversed the inhibitory effect of normorphine. Lowering the concentration of Ca2+ ions (from 2.5 to 1 mM) or increasing the concentration of Mg2+ ions (from 1.2 to 4.8 mM) in the bathing solution reduced the amplitude of e.j.p.s. Short trains of impulses (3Hz) facilitated the amplitude of successive e.j.p.s., probably by elevating the intracellular Ca2+ ion concentration. The inhibitory effect of normorphine upon these transients was inversely proportional to the length of the train. It is concluded that the reversal of the effect of normorphine by calcium does not occur at the level of the opiate receptor, and that the opiate depresses the stimulated release of the excitatory transmitter by a reduction in the supply of Ca2+ ions to the stimulus-release coupling mechanism in the sympathetic nerve terminals.
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009451:Neuroeffector Junction / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D014649:Vas Deferens / Q000294:innervation*
D000631:Aminopyridines; D009270:Naloxone; D009020:Morphine; D008274:Magnesium; D002118:Calcium