Motilin induces the endothelium-dependent relaxation of smooth muscle and the elevation of cytosolic calcium in endothelial cells in situ.
Using front-surface fluorometry with fura-2 and porcine aortic valvular strips, we investigated the effect of motilin, a gastrointestinal peptide, on the cytosolic Ca2+ concentration ([Ca2+]i) of endothelial cells in situ. Motilin induced a biphasic elevation of [Ca2+]i of the endothelial cells on the porcine aortic valvular strips. To investigate the physiological role of these Ca2+ transients in the endothelial cells, we determined the effect of motilin on [Ca2+]i as well as the tension of the smooth muscles in the porcine coronary strips with an intact endothelium. Motilin decreased [Ca2+]i and the tension of the coronary smooth muscle precontracted by U46619, a thromboxane A2 analogue, in an endothelium-dependent manner. In the presence of indomethacin (a cyclooxygenase inhibitor), motilin induced an endothelium-dependent relaxation of the coronary strips which was partially inhibited by N omega-nitro-L-arginine (L-NNA; a NO synthase inhibitor). These results thus indicate that motilin induces Ca2+ transients of the endothelial cells while it also induces vasorelaxation, which may be mediated by both L-NNA sensitive and resistant factors that are derived from the endothelium.
Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
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Higuchi
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Nishimura
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Kanaide
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001021:Aortic Valve / Q000187:drug effects / Q000502:physiology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016257:Fura-2; D066298:In Vitro Techniques; D009037:Motilin / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013997:Time Factors
D011450:Prostaglandin Endoperoxides, Synthetic; D019335:Nitroarginine; D009037:Motilin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D001120:Arginine; D002118:Calcium; D016257:Fura-2