1,2-Diacylglycerol, protein kinase C, and pancreatic enzyme secretion.
To determine the role of 1,2-diacylglycerol (1,2-DAG) and protein kinase C in pancreatic enzyme secretion, we measured the effect of various pancreatic secretagogues on the cellular mass of 1,2-DAG and amylase release in dispersed pancreatic acini from the guinea pig. In addition, we measured the effect of a recently described protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) (Hidaka, H., Inagaki, M., Kawamoto, S., and Sasaki, Y. (1984) Biochemistry 23, 5036-5041), on secretagogue-stimulated amylase release from the acini. Cholecystokinin-octapeptide (CCK-OP), cholecystokinintetrapeptide, and carbachol each increased 1,2-DAG 2-3-fold but the increases occurred only with concentrations of these secretagogues that were supramaximal for amylase release and that had an inhibitory effect on stimulated amylase release. Supramaximal concentrations of bombesin stimulated only a small increase in 1,2-DAG and did not cause inhibition of stimulated amylase release. When the action of carbachol was terminated with atropine or CCK-OP with dibutyryl cyclic GMP, stimulated amylase release ceased immediately but cellular 1,2-DAG required at least 15 min to return to the basal level. Increasing cytosolic free Ca2+ with the Ca2+ ionophore, A23187, in Ca2+-containing incubation media augmented amylase release stimulated by 4 beta-phorbol 12-myristate 13-acetate but inhibited amylase release stimulated by CCK-OP, carbachol, and bombesin without decreasing the cellular content of 1,2-DAG. H-7 inhibited protein kinase C activity in a pancreatic homogenate but augmented amylase release from acini stimulated by either CCK-OP, carbachol, or 4 beta-phorbol 12-myristate 13-acetate. These findings indicate that 1,2-DAG and protein kinase C do not have a stimulatory role in pancreatic stimulus-secretion coupling but may have an inhibitory one.
S J
SJ
Pandol
M S
MS
Schoeffield
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001839:Bombesin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013758:Tetragastrin / Q000494:pharmacology
D001095:Arachidonic Acids; D004075:Diglycerides; D005989:Glycerides; D007546:Isoquinolines; D010879:Piperazines; D013758:Tetragastrin; D016718:Arachidonic Acid; D003995:Dibutyryl Cyclic GMP; D000001:Calcimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002217:Carbachol; D011493:Protein Kinase C; D000681:Amylases; D012844:Sincalide; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin