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beta-Endorphin-induced stimulation of central sympathetic outflow: inhibitory modulation by central noradrenergic neurons

NM Appel and GR Van Loon

Endorphins, a class of endogenous opioid peptides, produce a diversity of physiological effects attributable to their actions in the central nervous system. We have reported previously the effect of intracisternal (i.c.) administration of synthetic human beta-endorphin to increase plasma catecholamine concentrations, presumably by acting at opioid receptors in the brain to stimulate the central sympathetic outflow to adrenal medulla and peripheral sympathetic nerve terminals. This beta-endorphin-induced increase in plasma catecholamine concentration is dose-dependent, inhibited by naloxone and blocked by bilateral adrenal gland denervation or ganglionic blockade with chlorisondamine. We also provided evidence supporting involvement of central cholinergic, somatostatin and angiotensin II neuronal systems in modulating this beta-endorphin-induced effect. In this study we examined the possibility of central noradrenergic regulation of beta- endorphin-induced catecholamine secretion. Simultaneous i.c. administration of norepinephrine with beta-endorphin blunted the plasma epinephrine response to i.c. beta-endorphin in conscious, unrestrained rats bearing chronic i.a. cannulas. On the other hand, depletion of brain norepinephrine by prior i.c. 6-hydroxydopamine (6-OHDA) treatment potentiated the plasma epinephrine response to i.c. beta-endorphin. In addition, rats pretreated with 6-OHDA appeared supersensitive to the blunting effect of i.c. norepinephrine on beta-endorphin-induced catecholamine secretion. Specifically, i.c. norepinephrine at a dose insufficient to reduce beta-endorphin-induced catecholamine secretion in vehicle-treated rats prevented beta-endorphin-induced epinephrine and norepinephrine secretion in rats whose brains had been depleted of norepinephrine by prior 6-OHDA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 237, Issue 3, pp. 695-701, 06/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics







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Copyright © 1986 by the American Society for Pharmacology and Experimental Therapeutics.