Presynaptic opiate receptor- and alpha 2-adrenoceptor-mediated inhibition of noradrenaline release in the rat brain: role of hyperpolarization?
The inhibitory actions of exogenous noradrenaline (1 microM) and clonidine (1 microM) as well as well as of the opiate receptor agonists morphine (1 microM) and [D-Ala2,D-Leu5]enkephalin (DADLE, 1 microM) on the potassium-induced Ca2+-dependent release of [3H]noradrenaline from superfused rat brain cortex slices were independent of the degree of depolarization when release was effected by 15 or 56 mM K+ for 5 min. The non-depolarization-dependent release of [3H]noradrenaline induced by exposing the slices for 5 min to medium with NaCl replaced by LiCl was only partially Ca2+-dependent and was not inhibited by the Ca2+ antagonist Cd2+ (50 microM). This release was strongly inhibited by morphine, DADLE, exogenous noradrenaline and clonidine at 1 microM concentrations both in the presence and the absence of extracellular Ca2+. Together with other data in the literature these results strongly suggest that opiate receptors and alpha 2-adrenoceptors located on noradrenergic axonal varicosities, unlike those located on cell bodies, do not primarily mediate hyperpolarization of the neuronal membrane. Instead the activation of these presynaptic receptors causes a reduction of Ca2+ availability for, or the utilization of Ca2+ by the secretion process upon invasion of an action potential.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013569:Synapses
D002121:Calcium Channel Blockers; D002712:Chlorides; D009294:Narcotics; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D008094:Lithium; D018021:Lithium Chloride; D003000:Clonidine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine; D010646:Phentolamine