Cholinergic stimulation of rat acinar cells increases c-fos and c-jun expression via a mitogen-activated protein kinase-dependent pathway.
Acetylcholine release from cholinergic neurons regulates pancreatic exocrine function through pathways that are still under investigation. Pancreatic AR42J acinar cells were studied to determine intracellular calcium ([Ca(2+)](i)) release, enzyme activation, and gene expression in response to the acetylcholine analog carbachol (CCh). CCh stimulated dose-dependent increases in [Ca(2+)](i) that were inhibited by atropine and by specific inhibitors to the muscarinic receptor subtypes m1 and m3. Polymerase chain reaction analysis was performed, which sequenced products corresponding to the m1 and m3 receptor subtypes but not the m2 subtype. CCh also stimulated mitogen-activated protein kinase activity. CCh induced time-and dose-dependent increases in the c-fos and c-jun early-response genes, which were blocked by m1 and m3 inhibition but not by m2 inhibition.
Turner
D J
DJ
Department of Surgery, University of Michigan, Ann Arbor, USA.
Cowles
R A
RA
Segura
B J
BJ
Mulholland
M W
MW
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology*; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015870:Gene Expression; D008969:Molecular Sequence Data; D010179:Pancreas / Q000166:cytology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012680:Sensitivity and Specificity
D018679:Cholinergic Agonists; D003959:Diamines; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011976:Receptors, Muscarinic; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; C054938:methoctramine; D002118:Calcium