tetrodotoxin and curarine

The regulatory system responsible for insulin oscillations from the in vitro pancreas is unknown. To test the hypothesis that intrapancreatic ganglia are the pacemaker or driver of the oscillations, combined nicotinic, muscarinic, and adrenergic antagonists were infused. Combined muscarinic, alpha- and beta-adrenergic, and presynaptic nicotinic receptor blockade (beta-bungarotoxin) was without effect on oscillations. The infusion of the postsynaptic nicotinic receptor antagonists, hexamethonium, alpha-bungarotoxin (ATX), or curarine, significantly altered the preinfusion oscillatory pattern of insulin release by reducing the period. Nicotine-stimulated insulin release was inhibited by ATX on a background of atropine, phentolamine, and beta-bungarotoxin. Propranolol decreased nicotine-stimulated insulin release, which was further reduced by ATX. These data support the theory that nicotinic receptors may be present pre- and postsynaptically at the ganglionic level and presynaptically on sympathetic nerve axons. We propose that ganglionic nicotinic receptors may be regulatory and that ganglia may serve as the pacemaker to regulate pancreatic hormone oscillations.

Topics: Animals; Atropine; Bungarotoxins; Dogs; Ganglia; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pancreas; Periodicity; Phentolamine; Propranolol; Receptors, Adrenergic; Receptors, Muscarinic; Receptors, Nicotinic; Tetrodotoxin; Tubocurarine