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- W4254927189 abstract "The effects of [Leu 13 ]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu 13 ]Motilin (0.1-10 nmol·kg -1 , i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol·kg -1 , [Leu 13 ]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla]betatrifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu 13 ]motilin. In contrast, hypotension induced by [Leu 13 ]motilin (1 nmol·kg -1 ) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10 -7 M), [Leu 13 ]motilin (10 -8 -10 -5 M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with N omega -nitro-L-arginine, a competitive inhibitor of NO synthase (10 -4 M). A high dose (10 -4 M) of GM-109 slightly decreased [Leu 13 ]motilin-induced relaxation, and shifted the concentration-response curve of [Leu 13 ]motilin to the right. However, the pA 2 value (4.09) of GM-109 for [Leu 13 ]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu 13 ]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.Key words: motilin, gastrointestinal motility, hypotension, hemodynamics, anesthetized dog, mesenteric artery, endothelium, nitric oxide." @default.
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- W4254927189 date "1998-12-01" @default.
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- W4254927189 title "Hypotensive mechanism of [Leu<sup>13</sup>]motilin in dogs in vivo and in vitro" @default.
- W4254927189 doi "https://doi.org/10.1139/y98-138" @default.
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