Effect of nicotine on exocytotic pancreatic secretory response: role of calcium signaling
More details
Hide details
Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, US
Formerly at Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical sciences, College of Medicine, Little Rock, US
Formerly in Medical Research, Central Arkansas Veterans Health Care System, Little Rock, US
Submission date: 2012-10-22
Acceptance date: 2013-01-16
Publication date: 2013-01-18
Corresponding author
Parimal Chowdhury   

Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, College of Medicine, 4301 W Markham Street, Little Rock 72205, Arkansas
Tobacco Induced Diseases 2013;11(January):1
Nicotine is a risk factor for pancreatitis resulting in loss of pancreatic enzyme secretion. The aim of this study was to evaluate the mechanisms of nicotine-induced secretory response measured in primary pancreatic acinar cells isolated from Male Sprague Dawley rats. The study examines the role of calcium signaling in the mechanism of the enhanced secretory response observed with nicotine exposure.

Isolated and purified pancreatic acinar cells were subjected to a nicotine exposure at a dose of 100 μM for 6 minutes and then stimulated with cholecystokinin (CCK) for 30 min. The cell’s secretory response was measured by the percent of amylase released from the cells in the incubation medium Calcium receptor antagonists, inositol trisphosphate (IP3) receptor blockers, mitogen activated protein kinase inhibitors and specific nicotinic receptor antagonists were used to confirm the involvement of calcium in this process.

Nicotine exposure induced enhanced secretory response in primary cells. These responses remained unaffected by mitogen activated protein kinases (MAPK’s) inhibitors. The effects, however, have been completely abolished by nicotinic receptor antagonist, calcium channel receptor antagonists and inositol trisphosphate (IP3) receptor blockers.

The data suggest that calcium activated events regulating the exocytotic secretion are affected by nicotine as shown by enhanced functional response which is inhibited by specific antagonists… 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. We conclude that nicotine plays an important role in promoting enhanced calcium levels inside the acinar cell.

Talamini G, Falconi M, Bassi C, Sartori N, Salvia R, Cadiron E, et al: Incidence of cancer in the course of chronic pancreatitis. Am J Gastroenterol. 1999, 94: 1253-1260. 10.1111/j.1572-0241.1999.01075.x.
Talamini G, Bassi C, Falconi M, et al: Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer. Dig Dis Sci. 1999, 44 (7): 1303-1311. 10.1023/A:1026670911955.
Lin Y, Tamakoshi A, Hayakawa T, Ogawa M, Ohno Y: Cigarette smoking as a risk factor for chronic pancreatitis: A case study in Japan. Pancreas. 2000, 21 (2): 100-114.
Maisonneuve P, Lowenfels AB, Mullhaupt B, Cavallini G, Lankisch PG, Anderson JR, Di-magno FP, Andren-Sandberg A, Demellof L, Frulloni L, Amman RW: Cigarette smoking accelerates progression of alcoholic chronic pancreatitis. Gut. 2005, 54: 446-447. 10.1136/gut.2004.048785.
Maisonneuve P, Lowenfels AB: Chronic pancreatitis and pancreatic cancer. Dig Dis. 2002, 20 (1): 32-37. 10.1159/000063165.
Lowenfels AB, Maisonneuve P: Risk factors for pancreatic cancer. J Cell Biochem. 2005, 95 (4): 649-656. 10.1002/jcb.20461.
Lau PP, Dubick MA, Yu GS, Morrill PR, Geokas MC: Dynamic changes of pancreatic structure and function in rats treated chronically with nicotine. Toxicol Appl Pharmacol. 1990, 3: 457-465.
Chowdhury P, Hosotani R, Chang LW, Rayford PL: Metabolic and pathologic effects of nicotine on the grastrointestinal tract and pancreas of rats. Pancreas. 1990, 5: 222-229. 10.1097/00006676-199003000-00016.
Chowdhury P, MacLeod S, Udupa KB, Rayford PL: Pathophysiological effects of nicotine on the pancreas: an update. Exp Biol Med. 2002, 227: 445-454.
Chowdhury P, Doi R, Tangoku A, Rayford PL: Structural and functional changes of rat pancreas exposed to nicotine. Int J Pancreatol. 1996, 18: 257-26.
Wittel UA, Hopt UT, Batra SK: Cigarette smoke-induced pancreatic damage: experimental data. Langenbecks Arch Surg. 2008, 393 (4): 581-588. 10.1007/s00423-007-0273-3.
Wittel UA, Pandey KK, Andrianifahanana M, Johansson SL, Cullen DM, Akhter MP, Brand RE, Prokopczyk B, Batra SK: Chronic pancreatic inflammation induced by environmental tobacco smoke inhalation in rats. Am J Gastroenterol. 2006, 101 (1): 148-159. 10.1111/j.1572-0241.2006.00405.x.
Hosotani R, Chowdhury P, McKay D, Rayford PL: Mechanism of action of nicotine on amylase release by isolated pancreatic acini. Pharmacol Biochem Behav. 1989, 3: 663-666.
Chowdhury P, Hosotani R, Rayford PL: Inhibition of CCK or carbachol-stimulated amylase release by nicotine. Life Sci. 1989, 45: 2163-2168. 10.1016/0024-3205(89)90083-0.
Brown P: The influence of smoking on pancreatic function in man. Med J Aust. 1976, 2 (8): 290-293.
Tai MH, Upham BL, Olson LK, Tsao MS, Reed DN, Trosko JE: Cigarette smoke components inhibited intercellular communication and differentiation in human pancreatic ductal epithelial cells. Int J Cancer. 2007, 120 (9): 1855-1862. 10.1002/ijc.22530.
Doi R, Chowdhury P, Nishikawa M, Takaori K, Inoue K, Imamura M, Rayford PL: Carbachol and cholecystokinin enhance accumulation of nicotine in rat acinar cells. Pancreas. 1995, 10: 154-160. 10.1097/00006676-199503000-00008.
Dellis O, Dedos SG, Tovey SC, Rahman T, Dubei SJ, Taylor CW: Ca2+ entry through plasma membrane IP3 receptors. Science. 2006, 313 (5784): 229-233. 10.1126/science.1125203.
Bootman MB, Collins TJ, Mackenzie L, Roderick ML, Berridge MJ, Peppiatt CM: 2-Aminoethoxy diphenyl borate (2-APB) is a reliable blocker of store operated Ca2+ entry but an inconsistent inhibitor of InsP3-induced Ca2+ release. FASEB J. 2002, 16 (10): 1145-1150. 10.1096/fj.02-0037rev.
Bowersox SS, Luther R: Pharmacotheraperutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom Conus magus. Toxicon. 1996, 36 (11): 1651-1858.
Jozef D, Kovaciko M, Sedek J, Koppel J, Sobel A, Chorvath B: The protein kinase C inhibitor H7 blocks phosphorylation of stathmin during TPA-induced growth inhibition of human pre-B leukemia REH6 cells. Leuk Res. 1995, 19 (7): 457-461. 10.1016/0145-2126(94)00154-3.
Reuhl TO, Amador M, Moorman JR, Pinkham J, Dani JA: Nicotinic acetylcholine receptors are directly affected by agents used to study protein phosphorylation. J Neurophysiol. 1992, 68: 407-416.
Rayford PL, Chowdhury P: Mecamylamine, s nicotinic receptor channel antagonist, affects amylase secretion by isolated pancreatic acinar cells. J Assoc Acad Minor Phys. 2001, 12 (1–2): 105-108.
Williams JA, Korc M, Dormer RL: Action of secretagogues on a new preparation of functionally intact isolated pancreatic acini. Am J Physiol. 1978, 235: E517-E524.
Hosotani R, Chowdhury P, McKay D, Rayford PL: Effect of L-364718, a new CCK antagonist, on amylase secretion in isolated pancreatic acini. Pancreas. 1988, 3: 95-98. 10.1097/00006676-198802000-00016.
Jung DH: Preparation and application of Procion yellow starch for amylase assay. Clin Chim Acta. 1980, 100: 7-11. 10.1016/0009-8981(80)90179-5.
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976, 72: 248-254. 10.1016/0003-2697(76)90527-3.
Bose C, Zhang H, Udupa KB, Chowdhury P: Activation of p-ERK1/2 by nicotine in pancreatic tumor cell line AR42J: effects on proliferation and secretion. Am J Physiol Gastrointestinal Liver Physiol. 2005, 289: G926-G934. 10.1152/ajpgi.00138.2005.
Chowdhury P, Bose C, Udupa KB: Nicotine-induced proliferation of isolated rat pancreatic acinar cells: effect on cell signalling and function. Cell Prolif. 2007, 40 (1): 125-141.
Chowdhury P, Walker A: A cell-based approach to study changes in the pancreas following nicotine exposure in an animal model of injury. Langenbecks Arch Surg. 2008, 93 (4): 547-555.
Majumdar APN, Vesenka GW, Dubick MA, Yu GSM, DeMorrow JM, Geokas MC: Morphological and biochemical changes of the pancreas in rat treated with acetaldehyde. Am J Physiol Gastrointest Liver Physiol. 1986, 250: G598-G606.
Wang XX, Zhu JH, Chen JZ, Shang YP: Effect of nicotine on the number and activity of circulating endothelial progenitor cells. J Clin Pharmacol. 2004, 44: 881-889. 10.1177/0091270004267593.
Russel MAH, Fayerabend C: Cigarette smoking. A dependence on high nicotine boli. Drug Metab Rev. 1978, 8: 29-57. 10.3109/03602537808993776.
Majumder APN, Davis GA, Dubick MA, Geokas MC: Nicotine stimulation of protein secretion from isolated rat pancreatic acini. Am J Physiol Gastrointest Liver Physiol. 1985, 248: G158-G163.
Nakayama H, Numakawa T, Ikeuchi T, Hatanaka H: Nicotine-induced phosphorylation of extracellular signalregulated protein kinase and CREB in PC12h cells. J Neurochem. 2001, 9: 489-498.
Chowdhury P, Udupa KB: Nicotine as mitogenic stimulus for pancreatic acinar cell proliferation. World J Gastroenterol. 2006, 12 (46): 7428-7432.
Piper A, Stryjek-Kaminska D, Klengel R, Zeuzem S: CCK, carbachol and bombesin activate distinct PLCisoenzymes via Gq/11 in rat pancreatic acinar membranes. Am J Physiol Gastrointest Liver Physiol. 1997, 272: G135-G140.
Wang J, Chen YB, Zhu XN, Chen RZ: Activation of p42/44 mitogen-activated protein kinase pathway in long-term potentiation induced by nicotine in hippocampal CA1 region in rats. Acta Pharmacol. 2001, 22: 685-690.
Wess J: G-protein coupled receptors: molecular mechanisms involved in receptor activation and selectivity of G-protein recognition. FASEB J. 1997, 11: 346-354.
Williams JA: Signal transduction and intracellular signaling in pancreatic acinar cells. Curr Opin Gastroenterol. 1995, 11: 397-401. 10.1097/00001574-199509000-00002.
Williams J: Intracellular signaling mechanisms activated by cholecystokinin-regulating synthesis and secretion of digestive enzymes in pancreatic acinar cells. Annu Rev Physiol. 2001, 63: 77-97. 10.1146/annurev.physiol.63.1.77.
Tang K, Wu H, Mahata SK, Mahata M, Gill BM, Parmer RJ, O’Connor DT: Stimulus coupling to transcription versus secretion in pheochromocytoma cells. Convergent and divergent signal transduction pathways and the crucial roles for route of cytosolic calcium entry and protein kinase. C J Clin Invest. 1997, 100: 1180-1192. 10.1172/JCI119630.
Zhang GH, Melvin JE: Nicotine increases [Ca2+]i in rat sublingual mucous acini by stimulating neurotransmitter release from presynaptic terminals. Proc Soc Exp Biol Med. 1994, 204: 292-301.
Mandic A, Victorson K, Strandberg L, Heiden T, Hansson J, Linder S, Shoshan MC: Calpain-mediated Bid cleavage and calpain-independent Bak modulation:two separate pathways in cisplatin-induced apoptosis. Mol Cell Biol. 2002, 22 (9): 3003-3013. 10.1128/MCB.22.9.3003-3013.2002.
Arany I, Megyesi JK, Kaneto H, Price PM, Safirstein RL: Cisplatin-induced cell death is EGFR/src/ERK signaling dependent in mouse proximal tubule cells. Am J Physiol Renal Physiol. 2004, 287: F543-F549. 10.1152/ajprenal.00112.2004.
Jaffe AB, Hall A: Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005, 21: 247-269. 10.1146/annurev.cellbio.21.020604.150721.
Sharma AK, Rohrer B: Calcium-induced calpain mediates apoptosis via caspase-3 in a mouse photoreceptor cell line. J Biol Chem. 2004, 279 (34): 35564-35573. 10.1074/jbc.M401037200.
Alznauer F, Conus S, Cavalli A, Folkers G, Simon HU: Calpain-1 regulates Bax and subsequent Smac-dependent caspase-3 activation in neutrophil apoptosis. J Biol Chem. 2004, 279: 5947-5957.
Social determinants of tobacco consumption among Nepalese men: findings from Nepal Demographic and Health Survey 2011
Vishnu Khanal, Mandira Adhikari, Sujan Karki
Harm Reduction Journal
The Pancreas
Uwe A. Wittel, Bradley R. Hall, Surinder K. Batra
Smoking and Pancreatic Disease
Mouad Edderkaoui, Edwin Thrower
Journal of Cancer Therapy
Chronic Nicotine Exposure In Vivo and In Vitro Inhibits Vitamin B1 (Thiamin) Uptake by Pancreatic Acinar Cells
Padmanabhan Srinivasan, Edwin C. Thrower, Gopalakrishnan Loganathan, A. N. Balamurugan, Veedamali S. Subramanian, Fred S. Gorelick, Hamid M. Said, Zoltán Rakonczay
Pathologic Cellular Events in Smoking-Related Pancreatitis
Edwin Thrower
Effects of Chronic Nicotine Administration on Salivary Gland in Mice: Immunohistochemical Study
Jung-Woo Jung, Jae-Kap Choi, Jin-Seok Byun
Journal of Oral Medicine and Pain
Epidemiologic and Mechanistic Associations Between Smoking and Pancreatitis
Julia B. Greer, Edwin Thrower, Dhiraj Yadav
Current Treatment Options in Gastroenterology
How does cigarette smoking cause acute pancreatitis?
Savio G. Barreto
Impact of Graphic Pack Warnings on Adult Smokers’ Quitting Activities: Findings from the ITC Southeast Asia Survey (2005–2014)
Lin Li, Ahmed I. Fathelrahman, Ron Borland, Maizurah Omar, Geoffrey T. Fong, Anne C. K. Quah, Buppha Sirirassamee, Hua-Hie Yong
Journal of Smoking Cessation
Pathophysiological Events Associated With Pancreatitis in Response to Tobacco
María Luaces-Regueira, Margarita Castiñeira-Alvariño, María Castro-Manzanares, Manuel Campos-Toimil, J. Enrique Domínguez-Muñoz
New Insights into Cellular Mechanisms in Smoking-Related Acute Pancreatitis
Wilson R Catapani
Gastroenterology & Hepatology : Open Accessg
Tobacco smoking and the risk of pancreatitis: A systematic review and meta-analysis of prospective studies
Dagfinn Aune, Yahya Mahamat-Saleh, Teresa Norat, Elio Riboli
Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas
Jagan Kalivarathan, Kunal Yadav, Will Bataller, Nathaniel Brigle, Mazhar Kanak
Investigation of The Role of Vagus in The Ameliorative Effect of Nicotine on Rat Pancreatitis Model
Meltem KOLGAZİ, Zozan GÜLEKEN, Bircan KOLBAŞI, Canberk BAŞIBÜYÜK, Feriha ERCAN, Berrak YEĞEN
Acibadem Universitesi Saglik Bilimleri Dergisi
Recurrence rates and risk factors for recurrence after first episode of acute pancreatitis: A systematic review and meta-analysis
Shuai Li, Lin Gao, Haowen Gong, Longxiang Cao, Jing Zhou, Lu Ke, Yuxiu Liu, Zhihui Tong, Weiqin Li
European Journal of Internal Medicine
Journals System - logo
Scroll to top