Amylin mobilizes [Ca2+]i and stimulates the release of pancreatic digestive enzymes from rat acinar AR42J cells: evidence for an exclusive receptor system of amylin.
Amylin dose-dependently stimulated the secretion of amylase and cholesterol esterase from rat pancreatic acinar AR42J cells. The biochemical basis of this action was investigated using fura-2-loaded AR42J cells. Amylin increased intracellular free calcium. [Ca2+]i, in a dose-dependent manner. The Ca2+ signal persisted even in Ca(2+)-free medium, suggesting mobilization from intracellular stores rather than influx. Consistently, thapsigargin abolished amylin-induced responses, suggesting that Ca2+ is released from an inositol 1,4,5-triphosphate (IP3)-sensitive pool. This was confirmed by the finding that amylin elevated IP3 levels. AR42J cells pretreated with amylin did not respond to amylin, suggesting that the receptors mediating this response undergo homologous desensitization. However, pretreatment with related peptides, calcitonin gene-related peptide (CGRP) and salmon calcitonin, did not diminish [Ca2+]i mobilization by amylin. CGRP and calcitonin also failed to mobilize [Ca2+]i even at 10 microM. These results suggests that the stimulatory effects of amylin on pancreatic digestive enzyme secretion from AR42J cells are mediated by a G-protein-linked membrane receptor coupled to IP3-dependent calcium pools.
Huang
Y
Y
Department of Surgery, University of Cincinnati Medical Center, OH 45267-0558, USA.
Fischer
J E
JE
Balasubramaniam
A
A
D000681:Amylases / Q000378:metabolism*; D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D058228:Islet Amyloid Polypeptide; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000378:metabolism*; D015398:Signal Transduction
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; D015544:Inositol 1,4,5-Trisphosphate; D002116:Calcitonin; D000242:Cyclic AMP; D000681:Amylases; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium