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

Stimulation of pancreatic nerves results in marked increases in exocrine secretion. However, the neurotransmitters and pre- and postsynaptic receptors, which determine synaptic transmission between nerves and acinar cells, are poorly defined. We used rabbit pancreatic lobules, which contain nerve terminals and secrete independently of the influences of vascular perfusion or gastrointestinal hormones, to study the role of cholinergic and noncholinergic nerves in regulating amylase secretion. Pancreatic nerves were stimulated by veratridine (Ver; 50-200 mu M), an activator of voltage-dependent sodium channels, in a concentration-dependent and tetrodotoxin-sensitive manner, resulting in an increase of 138 +/- 15% in amylase secretion above basal at 100 mu M. This stimulation was unaffected by either hexamethonium (100 mu M) or the combination of phentolamine and propranolol (10 mu M). Atropine (5 mu M) inhibited Ver-stimulated secretion by similar to 65-70%. Bethanechol (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-diphenylacetoxy-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 concentrations that had no significant effect on Bch-stimulated secretion. Thus cholinergic nerves, activating postsynaptic M-3, receptors, provided the predominant stimulatory innervation of rabbit pancreatic acini. Nonadrenergic, noncholinergic nerves also made a significant contribution to secretion. Adrenergic nerves did not appear to innervate acini or the excitatory cholinergic nerves directly.