Interaction between the inhibitory action of acetylcholine and the alpha-adrenoceptor autoinhibitory feedback system on release of [3H]-noradrenaline from rat atria and rabbit ear artery.
Stimulation-induced increases in the efflux of radioactivity (S-I efflux) were measured in the bathing medium following labelling of the noradrenergic transmitter pools of rat atria and rabbit artery preparations with [3H]-noradrenaline. In atria stimulated with trains of 16 or 60 pulses at 2 Hz, phentolamine enhanced, whereas acetylcholine inhibited S-I efflux. With trains of 16 pulses phentolamine had a smaller enhancing effect than with trains of 60 pulses, whereas the inhibitory effect of acetylcholine was more pronounced with 16 pulses of stimulation. The inhibitory effect of acetylcholine was markedly enhanced by phentolamine when stimulation was with 60 pulses. With 16 pulses of stimulation the effect of acetylcholine was unaltered by phentolamine and abolished by the alpha 2-adrenoceptor agonist 3,4-dihydroxyphenylimino-2-imidazolidine (DPI). Phentolamine had no effect on the negative inotropic effect of acetylcholine on driven left atrial preparations. In arterial preparations stimulated with trains of 30 pulses at 1 Hz, both acetylcholine and clonidine inhibited S-I efflux, whereas yohimbine and idazoxan enhanced S-I efflux. Combining acetylcholine with clonidine did not alter the inhibitory effect of clonidine but the combination of acetylcholine with yohimbine or idazoxan abolished the marked enhancing effects of yohimbine or idazoxan on S-I efflux. These findings indicate that there may be a reciprocal interaction between prejunctional alpha-adrenoceptors and prejunctional muscarinic cholinoceptors.
Loiacono
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RE
Rand
M J
MJ
Story
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DF
D000109:Acetylcholine / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000378:metabolism; D002395:Catecholamines / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004423:Ear / Q000098:blood supply*; D004558:Electric Stimulation; D005246:Feedback; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D019329:Idazoxan; D048288:Imidazolines; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D004146:Dioxanes; D048288:Imidazolines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C011775:(3,4-dihydroxyphenylamino)-2-imidazoline; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine; D019329:Idazoxan; D010646:Phentolamine