Phenylethylamine-induced release of noradrenaline fails to stimulate alpha 1-adrenoceptors modulating [3H]-acetylcholine release in rat atria, but activates alpha 2-adrenoceptors modulating [3H]-serotonin release in the hippocampus.
The modulation of the depolarization induced release of [3H]-acetylcholine by agonists acting on alpha-adrenoceptors was studied in superfused rat atrial slices. In this model, noradrenaline and methoxamine, but not UK 14304 reduced the potassium evoked release of [3H]-acetylcholine. The inhibitory action of these drugs was antagonized by the alpha 1 selective adrenoceptor antagonist prazosin. Propranolol, idazoxan and sulpiride did not antagonize the inhibition by noradrenaline of the potassium-evoked release of [3H]-acetylcholine. Exposure to amphetamine, beta-phenylethylamine, m- or p-tyramine, increased in a concentration-dependent manner the spontaneous outflow of [3H]-noradrenaline from atrial slices. Yet, these concentrations of the indirectly acting sympathomimetic amines, tested in the presence of an inhibitor of monoamine oxidase (MAO), failed to modify the potassium evoked release of [3H]-acetylcholine. Desipramine 3 mumol/l or cocaine 10 mumol/l did not affect the release of [3H]-acetylcholine evoked by potassium stimulation. Under similar experimental conditions, beta-phenylethylamine facilitated the spontaneous outflow of [3H]-noradrenaline, and inhibited the electrically-evoked release of [3H]-serotonin from the hippocampus by activation of alpha 2-adrenoceptors. It is concluded that the release of acetylcholine from atrial cholinergic neurons can be modulated through inhibitory alpha 1-adrenoceptors, which are not activated when the release of noradrenaline is induced by indirectly acting sympathomimetic amines. In addition, amphetamine or structurally related amines do not activate directly recognition sites in the cholinergic postganglionic parasympathetic neuron to modify the release of [3H]-acetylcholine.
D000109:Acetylcholine / Q000378:metabolism*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D006321:Heart / Q000187:drug effects; D006325:Heart Atria; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D014439:Tyramine / Q000494:pharmacology
D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; C029261:phenethylamine; D012701:Serotonin; D000661:Amphetamine; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine; D014439:Tyramine