A proposed mechanism for the potentiation of cAMP- mediated acid secretion by carbachol

Yuko Muto; Taku Nagao; Maki Yamada; Katsuhiko Mikoshiba; Tetsuro Urushidani

$Abstract Acid secretion in isolated rabbit gastric glands was monitored by the accumulation of 14 Caminopyrine. Stimulation of the glands with carbachol synergistically augmented the response to dibutyryl cAMP. The augmentation persisted even after carbachol was washed out and was resistant to chelated extracellular Ca 2+ and to inhibitors of either protein kinase C or calmodulin kinase II. Cytochalasin D at 10 μM preferentially blocked the secretory effect of carbachol and its synergism with cAMP, whereas it had no effect on histamine- or cAMP-stimulated acid secretion within 15 min. Cytochalasin D inhibited the carbachol-stimulated intracellular Ca 2+ concentration (Ca 2+ i ) increase due to release from the Ca 2+ store. Treatment of the glands with cytochalasin D redistributed type 3 inositol 1,4,5-trisphosphate receptor (the major subtype in the parietal cell) from the fraction containing membranes of large size to the microsomal fraction, suggesting a dissociation of the store from the plasma membrane. These findings suggest that intracellular Ca 2+ release by cholinergic stimulation is critical for determining synergism with cAMP in parietal cell activation and that functional coupling between the Ca 2+ store and the receptor is maintained by actin microfilaments. inositol 1,4,5-trisphosphate receptor cytoskeleton cytochalasin D calcium parietal cell rabbit Footnotes This work was supported in part by Japanese Ministry of Education, Science, Sports, and Culture Grants 10557219 and 11672160. Address for reprint requests and other correspondence: T. Urushidani, Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Univ. of Tokyo, Tokyo 113-0033, Japan (E-mail: urushi@mol.f.u-tokyo.ac.jp ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 2001 the American Physiological Society$

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A proposed mechanism for the potentiation of cAMP- mediated acid secretion by carbachol

Muto, Yuko; Nagao, Taku; Yamada, Maki; Mikoshiba, Katsuhiko; Urushidani, Tetsuro

Follow AJP - Cell Physiology , Volume 280 (1): C155 The American Physiological Society – Jan 1, 2001

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A proposed mechanism for the potentiation of cAMP- mediated acid secretion by carbachol

Muto, Yuko; Nagao, Taku; Yamada, Maki; Mikoshiba, Katsuhiko; Urushidani, Tetsuro

Follow AJP - Cell Physiology , Volume 280 (1): C155 The American Physiological Society – Jan 1, 2001

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