Modulation of insulin secretion by pancreatic ganglionic nicotinic receptors.
Autonomic ganglia may be regulated, in part, by nicotinic receptors. To test whether basal insulin secretion may be modulated by an endogenous pancreatic ganglionic mechanism, the effects of ganglionic pre- and postsynaptic nicotinic receptor antagonism were studied in the in vitro canine pancreas. Combined infusion of atropine, phentolamine, and propranolol had no affect on insulin secretion (P less than .30). Presynaptic nicotinic receptor blockade by beta-bungarotoxin (beta-BuTX) in combination with atropine and phentolamine reduced mean insulin secretion (78 +/- 18 U/ml, P less than .0025) from preinfusion concentrations (287 +/- 43 U/ml). The decrease in insulin secretion resulting from BuTX, atropine, and phentolamine was prevented by the addition of either specific postsynaptic nicotinic receptor blockade by alpha-bungarotoxin (P less than .05) or propranolol (P less than .005). Because it is known that postsynaptic nicotinic receptor agonism may stimulate the intraganglionic release of norepinephrine, these results suggest that nicotinic receptors are present at the ganglionic level in the pancreas and modulate insulin secretion by a complex intraganglionic mechanism. The postulated ganglionic nicotinic receptor-mediated mechanism may operate by the interaction of a beta-adrenergic inhibitory component, which may be activated by intraganglionic norepinephrine, and a stimulatory nonmuscarinic nonadrenergic (possibly peptidergic) component, which may be activated in the absence of intraganglionic norepinephrine.
Stagner
J I
JI
Samols
E
E
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D004285:Dogs; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
D002038:Bungarotoxins; D006584:Hexamethonium Compounds; D007328:Insulin; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D001285:Atropine; D010646:Phentolamine