Veratridine-stimulated amylase secretion from rabbit pancreatic lobules: Role of cholinergic and noncholinergic receptors

Stimulation of pancreatic nerves results in marked increases in exocrine se cretion. However, the neurotransmitters and pre- and postsynaptic receptors , which determine synaptic transmission between nerves and acinar cells, ar e poorly defined. We used rabbit pancreatic lobules, which contain nerve te rminals and secrete independently of the influences of vascular perfusion o r gastrointestinal hormones, to study the role of cholinergic and noncholin ergic nerves in regulating amylase secretion. Pancreatic nerves were stimul ated by veratridine (Ver; 50-200 mu M), an activator of voltage-dependent s odium channels, in a concentration-dependent and tetrodotoxin-sensitive man ner, resulting in an increase of 138 +/- 15% in amylase secretion above bas al at 100 mu M. This stimulation was unaffected by either hexamethonium (10 0 mu M) or the combination of phentolamine and propranolol (10 mu M). Atrop ine (5 mu M) inhibited Ver-stimulated secretion by similar to 65-70%. Betha nechol (Bch; 0.01-100 mu M) increased amylase secretion in a concentration- dependent manner (EC50, 6.2 mu M), with a maximal stimulation of 177 +/- 15 % above basal. Antagonism of Bch-stimulated secretion with 4-diphenylacetox y-N-melhylpiperidine, pirenzepine (Pzp), or methoctramine (Met) resulted in IC, values of 7.9 nM, 282 nM, and 79.8 mu M, respectively. Ver-stimulated secretion was unaffected by Pzp (0.1 and 1 nM) or Met (1 and 100 nM) at con centrations that had no significant effect on Bch-stimulated secretion. Thu s cholinergic nerves, activating postsynaptic M-3, receptors, provided the predominant stimulatory innervation of rabbit pancreatic acini. Nonadrenerg ic, noncholinergic nerves also made a significant contribution to secretion . Adrenergic nerves did not appear to innervate acini or the excitatory cho linergic nerves directly.