Calyculin A, okadaic acid and W-7 interfere with a distal step in pancreatic acinar signal transduction.
The effects of the serine/threonine phosphatase inhibitors calyculin A, okadaic acid and the calmodulin antagonist W-7 on amylase secretion were studied in pancreatic acini. Calyculin A and okadaic acid dose-dependently inhibited amylase secretion to basal levels when stimulated with the intracellularly acting secretagogues thapsigargin, 8-br-cAMP or PMA. W-7 dose-dependently inhibited thapsigargin- or 8-br-cAMP-induced amylase secretion. In combination, thapsigargin, 8-br-cAMP and PMA induced amylase secretion comparable to the stimulation by cholecystokinin. Their effect was significantly inhibited by calyculin A, okadaic acid or W-7. These data imply that type 1- and 2b-phosphatases and calmodulin play a key role in the stimulation of exocrine pancreatic secretion at a distal step of both the Ca2+/IP3- and cAMP-mediated signal-transduction pathways.
Meyer-Alber
A
A
I. Department of Medicine, Christian-Albrechts-University, Kiel, Germany.
Fetz
I
I
Waschulewski
I H
IH
Höcker
M
M
Fölsch
U R
UR
Schmidt
W E
WE
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008297:Male; D008387:Marine Toxins; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology*; D010179:Pancreas / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D004988:Ethers, Cyclic; D008387:Marine Toxins; D010080:Oxazoles; D013449:Sulfonamides; D013729:Terpenes; D019319:Okadaic Acid; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014660:Vasoactive Intestinal Peptide; C017967:W 7; D019284:Thapsigargin; C059041:calyculin A; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D000681:Amylases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium