It has long been established that stimulation of enzyme secretions by secretagogues in pancreatic acini involves several second messenger pathways that are rapidly acti vated by G protein coupled receptors and changes in intracellular calcium concentration and may in volve a cell mediated intracellular selleck catalog Ca2 response. In this study, the suppression of the Inhibitors,Modulators,Libraries secretory responses by calcium selective antagonists as shown in Figures 2 and 3 indicates that enhanced secretion induced by nicotine is triggered via calcium activated process. Enhanced release of calcium at pharmacological doses of nicotine may lead to loss of pancreatic function resulting in pancreatic path ology. Thus the studies may be clinically relevant to the development of pancreatitis in smokers and will most likely be based on nicotine dose derived from the number of cigarettes smoked.

It has been reported that in rat sublingual mucous acini, nicotine first triggers the release of acetylcholine from pre synaptic nerve terminals, which then activates muscarinic receptors. Inhibitors,Modulators,Libraries In this study, we have observed that w conotoxin, a potent Q type calcium channel blocker, completely inhibited nicotine induced pancreatic secretion suggesting that the regulation of pancreatic secretion by nicotine is physiologically regu lated by a calcium mediated process. The current study has examined the specificity of Inhibitors,Modulators,Libraries the nicotinic receptor an tagonist in primary cells and has demonstrated that its effect on downstream events regulating exocrine secre tion is regulated by calcium activated events involving both intra and extracellular calcium mobilization.

It has been demonstrated that intracellular calcium signals are involved in a number of events, in cluding apoptotic pathways. While Ca2 could be released from the i stores, Ca2 also could enter from the extracellular space through membrane channels. Recently Inhibitors,Modulators,Libraries it has been shown that the activation of inositol 1, 4, 5 trisphosphate receptors, found at the cellular membrane, results in an elevation of I. The modulation of I influences the activation of calplain, which controls cell cycle regulation, differentiation and apoptosis. Activation of Inhibitors,Modulators,Libraries calpain from pro calpain leads to apoptosome formation by cleavage of Bid, which in turn regulates Bax and activates caspase 3. Conclusions In summary, our data suggest that calcium activated events regulating the exocytotic secretion are affected by nicotine inducing enhanced functional response as con firmed by the inhibitory actions of these specific selleck chemicals antag onists.The results implicate the role of nicotine in the mobilization of both intra and extracellular calcium in the regulation of stimulus secretory response of enzyme secretion in this cell system.