Presynaptic modulation by melatonin of the nicotine-induced calcium-dependent release of norepinephrine from rat vas deferens.
This study demonstrates that melatonin potentiates the nicotine-induced calcium-dependent release of [3H]-norepinephrine from the rat vas deferens. Slices of the prostatic portion of the rat vas deferens were labelled in vitro with [3H]-norepinephrine and superfused with physiological solution. Nicotine (1 mM, 4 min) induced a calcium-dependent release of norepinephrine during the first (N1 = 1.43 +/- 0.16%) and the second (N2 = 1.11 +/- 0.2%, n = 22) nicotine stimulations. The ratio N2/N1 between two consecutive periods of nicotine stimulations was: 0.84 +/- 0.09 (n = 22). Melatonin (10-300 nM) did not modify the spontaneous release of [3H]-norepinephrine but potentiated in a concentration-dependent manner the calcium-dependent release. The competitive melatonin receptor antagonist luzindole did not modify the calcium-dependent release of [3H]-norepinephrine when added alone but completely antagonized the potentiation of release elicited by melatonin, suggesting interaction at the level of a melatonin receptor. We conclude that melatonin potentiates the nicotine-evoked release of [3H]-norepinephrine in the rat vas deferens through activation of melatonin presynaptic heteroreceptors on noradrenergic nerves involved in a positive feedback mechanism. This mechanism may mediate the increase in sympathetic neurotransmission observed with melatonin in the vas deferens. We cannot exclude, however, an effect of melatonin on cellular proteins and enzymes associated with the exocytotic process, which directly or indirectly may lead to the facilitation of release.
Carneiro
R C
RC
Department of Pharmacology, Northwestern University Medical School, Chicago, Ill. 60611.
Markus
R P
RP
Dubocovich
M L
ML
D000818:Animals; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000032:analysis / Q000502:physiology*; D014316:Tritium; D014363:Tryptamines / Q000494:pharmacology; D014649:Vas Deferens / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
D017661:Receptors, Presynaptic; D014363:Tryptamines; D014316:Tritium; C057154:luzindole; D009538:Nicotine; D008550:Melatonin; D002118:Calcium; D009638:Norepinephrine