title: Prejunctional alpha-adrenoceptor-mediated inhibition of norepinephrine release in blood-perfused skeletal muscle in situ.
abstract: The influence of alpha-adrenoceptor antagonists on the overflow of endogenous norepinephrine (NE) and vasoconstrictor responses elicited by sympathetic nerve stimulation (1-4 Hz, 2 min) was investigated in desipramine-pretreated canine blood-perfused skeletal muscle in situ. The nonselective alpha-adrenoceptor antagonist phentolamine enhanced stimulation-evoked NE overflow and reduced vasoconstrictor responses concentration-dependently. Similar effects were obtained with phenoxybenzamine (irreversible alpha-adrenoceptor antagonist). Desipramine pretreatment attenuated the enhancement of stimulation-evoked NE overflow produced by phenoxybenzamine, indicating that phenoxybenzamine also inhibits neuronal uptake. The enhancement by phenoxybenzamine was independent of the stimulation frequency, suggesting a similar engagement of prejunctional alpha-adrenoceptor-mediated inhibition of transmitter release over the frequency range studied here. The alpha 2-selective adrenoceptor antagonist yohimbine enhanced nerve stimulation-evoked NE overflow at concentrations similar to those required to antagonize vasoconstrictor responses to exogenous NE; 10-fold higher concentrations were required, however, to antagonize nerve stimulation-induced vasoconstriction. The concept of a quantitatively important prejunctional alpha 2-adrenoceptor-mediated feedback inhibition of NE release in vivo is supported by our findings in the skeletal muscle vasculature. Postjunctional alpha 2-adrenoceptors appear to be preferentially activated by circulating catecholamines but also seem to be involved in the nervous control of vascular tone.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001769:Blood; D004285:Dogs; D005260:Female; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010477:Perfusion; D010643:Phenoxybenzamine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D015016:Yohimbine; D009638:Norepinephrine; D010646:Phentolamine