Mast Cell Degranulation Increases Mouse Mast Cell Protease 4-Dependent Vasopressor Responses to Big Endothelin-1 But Not Angiotensin I.

Autor:	Vincent L; Department of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada (L.V., C.L., M.L., P.D.-J.); PhenoSwitch Bioscience Inc., Sherbrooke, Quebec, Canada (H.G.); Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden (G.P.); Department of Innovative Medicine, Osaka Medical College, Osaka, Japan (S.T.); and Department of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, Quebec, Canada (R.D.)., Lapointe C; Department of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada (L.V., C.L., M.L., P.D.-J.); PhenoSwitch Bioscience Inc., Sherbrooke, Quebec, Canada (H.G.); Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden (G.P.); Department of Innovative Medicine, Osaka Medical College, Osaka, Japan (S.T.); and Department of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, Quebec, Canada (R.D.)., Lo M; Department of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada (L.V., C.L., M.L., P.D.-J.); PhenoSwitch Bioscience Inc., Sherbrooke, Quebec, Canada (H.G.); Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden (G.P.); Department of Innovative Medicine, Osaka Medical College, Osaka, Japan (S.T.); and Department of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, Quebec, Canada (R.D.)., Gagnon H; Department of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada (L.V., C.L., M.L., P.D.-J.); PhenoSwitch Bioscience Inc., Sherbrooke, Quebec, Canada (H.G.); Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden (G.P.); Department of Innovative Medicine, Osaka Medical College, Osaka, Japan (S.T.); and Department of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, Quebec, Canada (R.D.)., Pejler G; Department of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada (L.V., C.L., M.L., P.D.-J.); PhenoSwitch Bioscience Inc., Sherbrooke, Quebec, Canada (H.G.); Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden (G.P.); Department of Innovative Medicine, Osaka Medical College, Osaka, Japan (S.T.); and Department of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, Quebec, Canada (R.D.)., Takai S; Department of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada (L.V., C.L., M.L., P.D.-J.); PhenoSwitch Bioscience Inc., Sherbrooke, Quebec, Canada (H.G.); Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden (G.P.); Department of Innovative Medicine, Osaka Medical College, Osaka, Japan (S.T.); and Department of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, Quebec, Canada (R.D.)., Day R; Department of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada (L.V., C.L., M.L., P.D.-J.); PhenoSwitch Bioscience Inc., Sherbrooke, Quebec, Canada (H.G.); Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden (G.P.); Department of Innovative Medicine, Osaka Medical College, Osaka, Japan (S.T.); and Department of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, Quebec, Canada (R.D.)., D'Orléans-Juste P; Department of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada (L.V., C.L., M.L., P.D.-J.); PhenoSwitch Bioscience Inc., Sherbrooke, Quebec, Canada (H.G.); Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden (G.P.); Department of Innovative Medicine, Osaka Medical College, Osaka, Japan (S.T.); and Department of Surgery, Division of Urology, Université de Sherbrooke, Sherbrooke, Quebec, Canada (R.D.) labpdj@usherbrooke.ca.
Jazyk:	angličtina
Zdroj:	The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2021 Feb; Vol. 376 (2), pp. 213-221. Date of Electronic Publication: 2020 Nov 05.
DOI:	10.1124/jpet.120.000325
Abstrakt:	Mouse mast cell protease 4 (mMCP-4), the murine functional analog to the human chymase, is a serine protease synthesized and stored in mast cell secretory granules. Our previous studies reported physiologic and pathologic roles for mMCP-4 in the maturation and synthesis of the vasoactive peptide endothelin-1 (ET-1) from its precursor, big ET-1. The aim of this study was to investigate the impact of mast cell degranulation or stabilization on mMCP-4-dependent pressor responses after the administration of big ET-1 or angiotensin I (Ang I). In anesthetized mice, mast cell degranulation induced by compound 48/80 (C48/80) or stabilization by cromolyn enhanced or repressed, respectively, the dose-dependent vasopressor responses to big ET-1 in wild-type (WT) mice but not in mMCP-4 knockout mice in a chymase inhibitor (TY-51469)-sensitive fashion. In addition, mMCP-4-dependent hydrolysis of the fluorogenic substrate Suc-Leu-Leu-Val-Tyr-7-amino-4-methylcoumarin was depleted or enhanced in peritoneal mast cells isolated from mice pretreated with C48/80 or cromolyn, respectively. Furthermore, C48/80 or cromolyn markedly increased or abolished, respectively, ET-1 (1-31) conversion from exogenous big ET-1 in WT mice peritoneal fluid-isolated mast cells, in vitro . Finally, the vasopressor responses to Ang I were unaffected by mast cell activation or stabilization, whereas those induced by the angiotensin-converting enzyme-resistant Ang I analog, [Pro 11 , D-Ala 12 ] Ang I, were potentiated by C48/80. Altogether, the present study shows that mast cell activation enhances the mMCP-4-dependent vasoactive properties of big ET-1 but not Ang I in the mouse model. SIGNIFICANCE STATEMENT: The current work demonstrates a significant role for mast cell stability in the cardiovascular pharmacology of big endothelin-1 but not angiotensin I in the murine systemic circulation. (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze:	MEDLINE
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