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 cycloxygenase inhibitor), motilin induced an endothelium-dependent relaxation of the coronary strips which was partially inhibited by N^ω-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.