Oxyntomodulin increases intrinsic heart rate through the glucagon receptor

Physiological Reports

Auyon Mukharji³  Daniel J. Drucker²  Maureen J. Charron¹ 

[1] Departments of Biochemistry, Medicine, and Ob/Gyn and Women's Health, Albert Einstein College of Medicine, New York, New York;Department of Medicine, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Canada;Department of Biology, Williams College, Williamstown, Massachusetts

关键词: Beta block;    GLP‐1;    OXM;    sympathetic nervous system;   

DOI  :  10.1002/phy2.112

来源: Wiley

【 摘 要 】

Abstract

Two hormones from the gastrointestinal tract, glucagon and oxyntomodulin (OXM), vigorously elevate the intrinsic heart rate (I_HR) of mice. We have previously shown that OXM influences murine heart rate (HR) independent of the glucagon-like peptide 1 (GLP-1) receptor. Here, we demonstrate using radiotelemetry in mice deficient in the glucagon receptor (Gcgr −/−) that both OXM and glucagon require the glucagon receptor for their chronotropic effects on the heart. Furthermore, we found that other hormones associated with hunger and satiety (ghrelin, leptin, and PYY_3-36) had no effect on I_HR, while cholecystokinin moderately elevated the I_HR. Finally, the resting HR of Gcgr −/− mice was higher than in control mice (Gcgr +/+ and Gcgr +/−) at thermal neutral temperature (30°C). Using atropine, we demonstrated that Gcgr −/− mice have diminished parasympathetic (PNS) influence of the heart at this temperature. Gcgr −/− mice displayed a normal bradycardia as compared to controls in response to administration of either methacholine (to activate the muscarinic acetylcholine receptor) or methoxamine (to activate the baroreflex through agonism of the α1 adrenergic receptor agonist) suggesting that vagal pathways are intact in the Gcgr −/− mice. As OXM is an agonist of the GLP-1 receptor and Gcgr with antidiabetic activity, we suggest OXM may be an alternative to glucagon in the treatment of overdose of beta-blockers to elevate HR in clinical conditions.

【 授权许可】

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© 2013 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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