Document Detail


Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro.
MedLine Citation:
PMID:  10326832     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol x kg(-1), i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol x kg(-1), [Leu13]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] trifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol x kg(-1)) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10(-7) M), [Leu13]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 [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.
Authors:
T Iwai; H Nakamura; H Takanashi; K Yogo; K Ozaki; N Ishizuka; T Asano
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  76     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-06-30     Completed Date:  1999-06-30     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  CANADA    
Other Details:
Languages:  eng     Pagination:  1103-9     Citation Subset:  IM    
Affiliation:
Chugai Pharmaceutical Co. Ltd., Fuji-Gotemba Research Labs, Shizuoka, Japan. iwaitks@gt.chugai-pharm.co.jp
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MeSH Terms
Descriptor/Qualifier:
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
Animals
Dogs
Gastrointestinal Agents / antagonists & inhibitors,  pharmacology*
Gastrointestinal Motility / drug effects*
Hemodynamics / drug effects*
Hormone Antagonists / pharmacology
Hypotension / chemically induced
Male
Mesenteric Arteries / drug effects
Motilin / antagonists & inhibitors,  pharmacology*
Peptides, Cyclic / pharmacology
Receptors, Gastrointestinal Hormone / drug effects
Receptors, Neuropeptide / drug effects
Vasoconstrictor Agents / pharmacology
Chemical
Reg. No./Substance:
0/GM 109; 0/Gastrointestinal Agents; 0/Hormone Antagonists; 0/Peptides, Cyclic; 0/Receptors, Gastrointestinal Hormone; 0/Receptors, Neuropeptide; 0/Vasoconstrictor Agents; 0/motilin receptor; 52906-92-0/Motilin; 76898-47-0/15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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