{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T05:15:08Z","timestamp":1717996508455},"reference-count":24,"publisher":"American Physiological Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:p> In antral mucous cells, acetylcholine (ACh, 1 \u03bcM) activates Ca<jats:sup>2+<\/jats:sup>-regulated exocytosis, consisting of an initial peak that declines rapidly (initial transient phase) followed by a second slower decline (late phase) lasting during ACh stimulation. The addition of 8-bromo-cGMP (8-BrcGMP) enhanced the initial phase, which was inhibited by the protein kinase G (PKG) inhibitor guanosine 3\u2032,5\u2032-cyclic monophosphorothoiate, \u03b2-phenyl-1, N<jats:sup>2<\/jats:sup>-etheno-8-bromo, Rp-isomer, sodium salt (Rp-8-BrPETcGMPS, 100 nM). However, Rp-8-BrPETcGMPS produced a delayed, but transient, increase in the exocytotic frequency during the late phase that was abolished by a protein kinase A (PKA) inhibitor (PKI-amide), suggesting that Rp-8-BrPETcGMPS accumulates cAMP. The cGMP-dependent phosphodiesterase 2 (PDE2), which degrades cAMP, may exist in antral mucous cells. The PDE2 inhibitor BAY-60-7550 (250 nM) mimicked the effect of Rp-8-BrPETcGMPS on ACh-stimulated exocytosis. Measurement of the cGMP and cAMP contents in antral mucosae revealed that ACh stimulates the accumulation of cGMP and that BAY-60-7550 accumulates cAMP similarly to Rp-8-BrPETcGMPS during ACh stimulation. Analyses of Western blot and immunohistochemistry demonstrated that PDE2A exists in antral mucous cells. In conclusion, Rp-8-BrPETcGMPS accumulates cAMP by inhibiting PDE2 in ACh-stimulated antral mucous cells, leading to the delayed, but transient, increase in the frequency of Ca<jats:sup>2+<\/jats:sup>-regulated exocytosis. PDE2 may prevent antral mucous cells from excessive mucin secretion caused by the cAMP accumulation. <\/jats:p>","DOI":"10.1152\/ajpgi.00281.2012","type":"journal-article","created":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T08:53:17Z","timestamp":1362127997000},"page":"G773-G780","source":"Crossref","is-referenced-by-count":6,"title":["A PKG inhibitor increases Ca<sup>2+<\/sup>-regulated exocytosis in guinea pig antral mucous cells: cAMP accumulation via PDE2A inhibition"],"prefix":"10.1152","volume":"304","author":[{"given":"Saori","family":"Tanaka","sequence":"first","affiliation":[{"name":"Nakahari Project of Central Research Laboratory, Osaka Medical College, Takatsuki, Japan;"},{"name":"Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rina","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Nakahari Project of Central Research Laboratory, Osaka 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