Hypothalamic regulation of pancreatic secretion is mediated by central cholinergic pathways in the rat

The vago-vagal reflex plays an important role in mediating pancreatic secretion evoked by cholecystokinin and non-cholecystokinin-dependent luminal factors. We hypothesize that the vago-vagal reflex mediating pancreatic secretion in the rat is under central control and regulated by cholinergic pathways in the hypothalamus. To test this hypothesis, we demonstrated that chronic decerebration decreased basal pancreatic enzyme secretion from 318 ± 12 to 233 ± 9 mg h^-1 and reduced the net increase in pancreatic secretion stimulated by intraduodenal infusion of 5% peptone and hypertonic NaCl by 54% and 45%, respectively. Intracerebroventricular administration of methscopolamine (MSCP, 50 nmol (5 μl)^-1), a blood-brain barrier-impermeant cholinergic muscarinic receptor antagonist, evoked results similar to those achieved by chronic decerebration. To localize the sites of action, we demonstrated that microinjection of MSCP (20 nmol) into the lateral hypothalamic nucleus or the paraventricular nucleus resulted in inhibition of both basal pancreatic protein secretion and luminally stimulated pancreatic secretion by 48% and 52%, respectively. Intracerebroventricular injection of hemicholinium-3 at doses known to deplete the endogenous ACh store produced similar inhibitory results. In addition, microinjection of ACh (5 pmol) or the muscarinic M₁ receptor agonist McN-A-343 (30 ng) into the lateral hypothalamic nucleus increased pancreatic secretion over basal levels by 46% and 40%, respectively. Selective lesions of lateral septal cholinergic neurons decreased basal pancreatic secretion and inhibited peptone-induced pancreatic secretion by 30%. Destruction of the lateral parabrachial nucleus produced a 44% inhibition of peptone-induced pancreatic section. Finally, microinjection of glutamate into the lateral septum or the lateral parabrachial nucleus stimulated vagal pancreatic efferent nerve firings from a basal level of 0 ± 0.5 impulses (30 s) ^-1 to 4.5 ± 0.5 and 14 ± 2 impulses (30 s) ^-1, respectively, and pancreatic protein output increased 50% and 84% over basal levels. Administration of MSCP to the paraventricular nucleus eliminated these effects. These observations suggest that cholinergic neurons of the lateral septum and lateral parabrachial nucleus regulate pancreatic secretion. Further, cholinergic input from the lateral parabrachial nucleus to the hypothalamus plays a major role in the modulation of vagal pancreatic efferent nerve activity and pancreatic secretion evoked by the vago-vagal reflex. © The Physiological Society 2003.