Adrenergic and nonadrenergic cotransmitters inhibit insulin secretion during sympathetic stimulation in dogs.
Vascular and biochemical responses to pancreatic sympathetic nerve stimulation were investigated in the blood-perfused pancreas of anesthetized dogs. During sympathetic nerve stimulation, pancreatic perfusion pressure and norepinephrine release increased, whereas insulin secretion decreased. The latter effect did not occur after pretreatment with the alpha 2-adrenoceptor antagonist idazoxan. However, after beta-adrenoceptor blockade with propranolol, neither single administration of idazoxan nor the alpha 1-adrenoceptor antagonist prazosin or glibenclamide, a blocker of ATP-modulated K+ channels, affected the decrease in insulin secretion induced by sympathetic nerve stimulation. In contrast, the combination of glibenclamide with idazoxan markedly antagonised the decrease in insulin release evoked by the latter procedure. After depletion of catecholamines with syrosingopine, the stimulation-induced inhibition of insulin secretion remained unchanged even though no increases in pancreas perfusion pressure or norepinephrine release were observed. In this preparation, glibenclamide inhibited the decrease in insulin release by 50%. In animals pretreated with the neuronal blocking agent bretylium, all of the responses to sympathetic nerve stimulation were abolished. These results indicate that the inhibitory effects exerted by the sympathetic nervous system on insulin secretion are mediated not only by the classical neurotransmitter norepinephrine acting on alpha 2-adrenoceptors but also by a nonadrenergic cotransmitter that can maintain transmission under conditions of catecholamine deficiency. The postulated nonadrenergic cotransmitter(s) acts, at least partly, via the opening of ATP-modulated K+ channels blockable by glibenclamide, and its release can be prevented by the neuronal blocking agent bretylium.
Lorrain
J
J
Synthélabo Recherche (L.E.R.S.), Bagneux, France.
Angel
I
I
Duval
N
N
Eon
M T
MT
Oblin
A
A
Langer
S Z
SZ
D000818:Animals; D001949:Bretylium Compounds / Q000494:pharmacology; D004285:Dogs; D004338:Drug Combinations; D004558:Electric Stimulation; D004837:Epinephrine / Q000502:physiology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology
D001949:Bretylium Compounds; D004338:Drug Combinations; D007329:Insulin Antagonists; D018377:Neurotransmitter Agents; D013566:Sympathomimetics; D012110:Reserpine; C045166:bretylium; D005905:Glyburide; D004837:Epinephrine