Calyculin A, a phosphoprotein phosphatase inhibitor, stimulates acid secretion in isolated gastric glands.
The effects of pkadaic acid (OKA) and calyculin A (CLA), inhibitors of protein phosphatases type 1 (PrPase1) and type 2A (PrPase2A), an acid secretion were examined in rabbit isolated gastric gland, CLA, but not OKA, strongly stimulated acid secretion by itself without affecting glandular adenosine 3',5'-cyclic monophosphate (cAMP) contents. CLA-induced secretion was suggested to be mainly due to the increase in the phosphorylation of protein kinase A substrates via the inhibition of PrPase1 in the parietal cell, since 1) CLA-induced secretion was not inhibited by cimetidine or atropine, 2) a protein kinase A inhibitor inhibited the secretion, whereas a protein kinase C inhibitor did not, 3) CLA augmented dibutyryl cAMP-induced secretion in some cases, and 4) OKA, which is 100 times more selective to PrPase2A than to PrPase1, was not a secretagogue. Unexpectedly, CLA did not augment the secretion by histamine, possibly because the inhibitor augmented the phosphorylation-mediating negative feedback pathway as well. Both CLA and OKA markedly increased phosphorylation of ezrin, a putative protein kinase A substrate, in the course of secretory activation.
Urushidani
T
T
Department of Cell Biology, University of Tsukuba, Ibaraki, Japan.
Nagao
T
T
D009597:4-Nitrophenylphosphatase / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D066298:In Vitro Techniques; D008387:Marine Toxins; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D013268:Stimulation, Chemical
D008387:Marine Toxins; D010080:Oxazoles; D011506:Proteins; D019319:Okadaic Acid; C059041:calyculin A; D000242:Cyclic AMP; D010749:Phosphoprotein Phosphatases; D009597:4-Nitrophenylphosphatase