Pulse duration and alpha 2-adrenoceptors modify noradrenaline release from field-stimulated atria.
In guinea-pig atria preloaded with 10 muCi [3H]noradrenaline, field stimulation during the refractory period increased the release of radioactivity and the force of contraction. Both effects were dependent on the extracellular Ca2+ concentration and were abolished by 3 x 10(-8) mol/l tetrodotoxin. When applied during each refractory period, two short (0.05 ms) pulses released significantly more radioactivity than one pulse of 0.1 ms duration applied during each refractory period. Similarly, a train of four pulses (0.05 ms each) was more effective than one pulse lasting 0.2 ms. The radioactivity released by single, long-lasting pulses in each refractory period was increased by phentolamine, idazoxan and N-ethylmaleimide. A small increase was also obtained with prazosin. The effect of phentolamine was antagonized by clonidine but not by phenylephrine. Clonidine did not prevent the effect of N-ethylmaleimide (all drugs 3 x 10(-5) mol/l; atropine 10(-7) mol/l and cocaine 3 x 10(-6) mol/l present in all experiments). It is concluded that activation of prejunctional alpha 2-adrenoceptors reduces the amount of noradrenaline release by one long field pulse in each refractory period. In most experiments, the inotropic effect of the two stimulation protocols was not significantly different. However, when atria were stimulated with four pulses immediately before stimulation with one pulse, the autoinhibition thus caused was strong enough to also reduce the inotropic effect of this stimulation protocol.
Brasch
H
H
Department of Pharmacology, Medical University of Lübeck, F.R.G.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005033:Ethylmaleimide / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D013779:Tetrodotoxin; D003000:Clonidine; D005033:Ethylmaleimide; D002118:Calcium; D009638:Norepinephrine