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A PKG Inhibitor Increases Ca(2+)-regulated Exocytosis in Guinea Pig Antral Mucous Cells: cAMP Accumulation via PDE2A Inhibition

A PKG Inhibitor Increases Ca(2+)-regulated Exocytosis in Guinea Pig Antral Mucous Cells: cAMP Accumulation via PDE2A Inhibition

Saori Tanaka, Rina Tanaka, Saeko Harada, Yuka Kohda, Hitoshi Matsumura, Chikao Shimamoto, Yukinori Sawabe, Yoshinori Marunaka, Hiroko Kuwabara, Yuko Takahashi, Shigenori Ito, Takashi Nakahari

Am J Physiol Gastrointest Liver Physiol. 2013 May 1;304(9):G773-80.

PMID: 23449671

Abstract:

In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca(2+)-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',5'-cyclic monophosphorothoiate, β-phenyl-1,N(2)-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(2+)-regulated exocytosis. PDE2 may prevent antral mucous cells from excessive mucin secretion caused by the cAMP accumulation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP172806201	Guanosine 3ʹ,5ʹ-cyclic Monophosphorothioate, β-Phenyl-1,N²-etheno-8-bromo-, Rp-Isomer, Sodium Salt - CAS 172806-20-1		172806-20-1	Price

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