[Google Scholar]Wiley RG

[Google Scholar]Wiley RG. 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. Tenapanor 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. Exocrine pancreatic secretion is largely controlled by the autonomic nervous system. We and other investigators have clearly demonstrated that the vago-vagal reflex plays a crucial role in the mediation of postprandial pancreatic enzyme secretion. Previous studies in the rat showed that cholecystokinin (CCK) (Li & Owyang, 19931997) and luminal non-CCK-dependent factors (Li & Owyang, 19962000). Although pancreatic secretion can be mediated by vago-vagal reflexes located within the brainstem, these reflexes may be modulated by input from higher centres (Rogers 1996). It has been recognized since Pavlov’s time (Pavlov, 1910) that the CNS exerts considerable control over the cephalic phase of pancreatic secretion (Sarles 1968). The hypothalamus receives a wide variety of convergent afferent inputs from the viscera and regulates autonomic activities by modulating neuronal input to Tenapanor autonomic preganglionic neurons. With the exception of the pioneering work of Gilsdorf (1966), which suggested the involvement of the hypothalamus in regulating pancreatic secretion, the physiological significance of forebrain input in the mediation of postprandial pancreatic secretion has remained largely unexplored. Muscarinic receptors are widely distributed in the brain, including the hypothalamus and the vagal nucleus, and central muscarinic actions are potentially widespread (Whittaker, 1988). Previous studies have shown that the central cholinergic pathway contributes significantly to the regulation of digestive functions, including salivation (Tomic-Beleslin & Beleslin, 1986), gastric secretion (Grill & Norgren, 1978), gastric dysrhythmias (Hasler 1995), emesis (Pedigo & Brizzee, 1985), and the oesophagomotor response (Lu & Bieger, 1998). Endocrine pancreatic polypeptide (PP) cells within the pancreatic islets and scattered throughout the exocrine tissue synthesize and release PP (Taylor, 1989). The plasma PP response is a reliable index of vagal cholinergic input to the pancreas. Infusion of atropine into the lateral cerebral ventricle is known to abolish fluctuations of basal PP levels and also PP secretion stimulated by hypoglycaemia or food intake (Okita 1997), which suggests involvement of the central muscarinic cholinergic system in the regulation of vagal efferent input to the pancreas. We have shown that peripheral cholinergic blockade completely abolishes pancreatic secretion (Li & Owyang, 19931990). We hypothesize that involvement of the vago-vagal reflex in mediating pancreatic secretion is under central control and Mouse monoclonal to MPS1 regulated by cholinergic pathways in the hypothalamus. In this study, we performed pancreatic secretion studies in the conscious rat and investigated the effects of chronic decerebration on basal and stimulated pancreatic enzyme secretion. To localize the sites of action, we examined the effects of microinjection of methscopolamine (MSCP) into the dorsal motor nucleus of the vagus (DMV), Tenapanor the lateral hypothalamic nucleus (LH) and the paraventricular nucleus (PVN) on pancreatic secretion evoked by luminal stimuli. In addition, we investigated the role of endogenous ACh on basal and stimulated pancreatic secretion by administration of intracerebroventricular (I.C.V.) injections of hemicholinium-3 at doses known to deplete the endogenous ACh store. To identify the sites of cholinergic neurons responsible for modulating pancreatic secretion, we examined the effects of.