As shown in panel A, the basal levels of amylase release were simi lar in all four groups. Upon stimulation with CCK 8 definitely levels of amylase release were enhanced significantly in all groupss. Treatment with nicotine induced CCK sti mulated levels more than the control group. However, in the presence of JNK inhibitor, or p 38 kinase inhibitor, the enhanced response induced by nicotine was not changed. The response of acinar cell to amylase release by nicotine in the presence of JNK inhibitor is identical to that of p 38 kinase inhibitor. Discussion The data presented in this communication demonstrates, Inhibitors,Modulators,Libraries in part, the mechanism by which nicotine induced the enhanced secretory response in pancreatic acinar cells In earlier studies the effect of nicotine on cell signal ing and function in this cell system and in rat tumori genic cell line has been reported from this laboratory.

However, the precise mechanism by which nicotine induces the enhancement of the acinar cell function was not shown. The initial focus of the current study was to confirm the effects of nicotine on stimu lated secretory response in primary cells and then Inhibitors,Modulators,Libraries to evaluate its mechanism. As shown in Figures, nicotine treatment maximally increased basal and CCK stimulated enzyme secretions at 6 min of nicotine ex posure. The dose of nicotine used for the study was identical to that was used in our earlier reported studies. The selection of the nicotine dose was based on published literature reported both in in vivo and other cell culture studies.

Dose levels of nicotine used in our study were below peak plasma nicotine Inhibitors,Modulators,Libraries concentration found Inhibitors,Modulators,Libraries in chronic cigarette smo kers, which ranges from 10 to 15 mM, measured within 20 min of cigarette smoking. In addition, in other laboratories, nicotine doses at varying concentration ranging from 0. 75 mM to 25 mM have been used in iso lated rat pancreatic acini. In our current study, a lower nicotine dose of 100 uM, was used resulting in an induction of maximal secretory response when exposed for 3 min, which persisted for 6 min before decreasing. This is consistent with our findings published earlier. We have reported earlier that nicotine acts as a mito gen in acinar cell system by activating p ERK 1 and 2.

Our studies show that ERK12 is activated by nicotine treatment under similar conditions and in the presence of the nicotine receptor antagonist the stimula tory cell response remain unaffected, implying that the kinase and secretory responses induced by nicotine are completely independent of each other and, perhaps, in volve a separate mechanism. In this study we have Inhibitors,Modulators,Libraries looked into the influence of MAPK activation by nico tine and its effects on cell function. As shown in Figures 4 and 5, mitogen activated protein kinases have no influence on selleck screening library nicotine induced CCK stimulated cell function sug gesting that response of nicotine on cell function is regu lated by a mechanism not related to MAPK activation.