Endocrinology, Vol 124, 3117-3121, Copyright © 1989 by Endocrine Society

ARTICLES

Alpha 2-adrenergic stimulation counteracts the metabolic effects of vasoactive intestinal peptide in isolated rat enterocytes

H Vidal and JP Riou
Institut National de la Sante et de la Recherche Medicale, Faculte de Medecine Alexis Carrel, Lyon, France.

The purpose of this investigation was to determine if alpha 2- adrenergic receptor activation suppresses the effects of vasoactive intestinal peptide (VIP) on glucose and fatty acid metabolism in isolated rat enterocytes. VIP (10(-7) M) produced an acute 40% inhibition of glucose oxidation and a 115% stimulation of palmitate oxidation. Addition of epinephrine (10(-6) M) together with propranolol (10(-6) M) to avoid interference with beta-adrenoreceptors did not affect basal glucose and palmitate oxidation, but suppressed the effects of VIP by more than 90%. The inhibition by VIP of pyruvate dehydrogenase and acetylcoenzyme-A carboxylase, the enzymes considered as the target sites for the neuropeptide, was also abolished by epinephrine. We assumed that epinephrine acted through the stimulation of alpha 2-adrenergic receptors, since 1) epinephrine suppressed VIP- induced accumulation of cAMP in the cells; and 2) the alpha 2-agonist clonidine (10(-6) M) reproduced epinephrine effects, whereas they were abolished by the alpha 2-antagonist yohimbine (10(-6) M). These findings strengthen the assumption that VIP controls glucose and fatty acid metabolism by a cAMP-dependent mechanism and demonstrate, for the first time, that the contribution of substrates as energy fuel is under dual neurohormonal regulation by VIP and catecholamines in isolated rat enterocytes.