Calyculin a, a phosphoprotein phosphatase inhibitor, stimulates
acid secretion in isolated gastric glands.
Nagao, Tetsuro Urushidani Taku.
Department of Cell Biology, Institute of Basic Medical Sciences,
University of Tsukuba, Tsukuba, Ibaraki, 305, Japan, and Department
of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences,
The University of Tokyo, Hongo, Tokyo, 113, Japan
APStracts 2:0138G, 1995.
The effects of okadaic acid (OKA) and calyculin A (CLA), inhibitors of
protein phosphatases type 1(PrPase1) and type 2A (PrPase2A), on acid
secretion were examined in rabbit isolated gastric glands. CLA, but
not OKA, strongly stimulated acid secretion by itself without
affecting glandular cyclic AMP contents. CLA-induced secretion was
suggested to be mainly due to the increase in the phosphorylation of
A-kinase substrates via the inhibition of PrPase 1 in the parietal
cell, since (1) CLA-induced secretion was not inhibited by cimetidine
or atropine, (2) an A-kinase inhibitor inhibited the secretion,
whereas a C-kinase inhibitor did not, (3) CLA augmented dibutyryl
cyclic AMP-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 A
-kinase substrate in the course of secretory activation.
Received 3 January 1995; accepted in final form 28 June 1995.
APS Manuscript Number G4-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.