PACAP-38 causes phospholipase C-dependent calcium signaling in rat acinar cell line.
BACKGROUND
Pituitary adenylate cyclase activating peptide (PACAP-38), a neuropeptide of the vasoactive intestinal peptide/secretin family, localizes to intrapancreatic neurons and stimulates exocrine secretion from the pancreas. PACAP-38 stimulates calcium signaling in the rat pancreatic cell line AR42J. The purpose of this study was to elucidate the mechanisms of PACAP-evoked calcium signaling in these cells.


METHODS
Continuous measurements of intracellular calcium were taken by fluorescent digital microscopy with the dye fura-2. Mechanisms of PACAP-38-evoked calcium signals were determined by a panel of inhibitors. Inositol phosphates production in response to PACAP-38 was measured. The ability of PACAP-38 to stimulate amylase release was used to determine a relevant dose range for these studies.


RESULTS
We have shown that (1) AR42J cells respond to PACAP-38 with biphasic increases in [Ca2+]i in a dose-dependent fashion; (2) PACAP-38 acts through phospholipase C to release inositol triphosphate (IP3)-sensitive Ca2+ stores with (3) a subsequent influx of extracellular Ca2+.


CONCLUSIONS
PACAP-38 activates calcium signaling through phospholipase C at concentrations that stimulate amylase release in AR42J cells.
Barnhart
D C
DC
Department of Surgery, University of Michigan, Ann Arbor, USA.
Sarosi
G A
GA
Mulholland
M W
MW
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002809:Chondroitin Sulfates / Q000494:pharmacology; D018274:Electroporation; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
C495403:Adcyap1 protein, rat; D007295:Inositol Phosphates; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D002809:Chondroitin Sulfates; D010738:Type C Phospholipases; D000681:Amylases; D002118:Calcium