Alpha 2-adrenergic stimulation counteracts the metabolic effects of vasoactive intestinal peptide in isolated rat enterocytes.
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.
Vidal
H
H
Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine Alexis Carrel, Lyon, France.
Riou
J P
JP
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D010169:Palmitic Acids; D011768:Pyruvate Dehydrogenase Complex; D011942:Receptors, Adrenergic, alpha; D019308:Palmitic Acid; D015016:Yohimbine; D014660:Vasoactive Intestinal Peptide; D011433:Propranolol; D000103:Acetyl-CoA Carboxylase; D003000:Clonidine; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine