Document Detail


The role of diacylglycerol as a modulator of oxytocin-stimulated phasic contractions in myometrium from pregnant and nonpregnant rats.
MedLine Citation:
PMID:  10764478     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The role of diacylglycerol in the phosphatidylinositol-signaling pathway is to activate protein kinase C. In the myometrium, protein kinase C activation leads to inhibition of phasic contractions. These studies are designed to determine why stimulation of the phosphatidylinositol-signaling pathway caused by oxytocin does not cause a paradoxical suppression of contractions through diacylglycerol production and protein kinase C activation. Specifically, these studies were performed to test the hypothesis that diacylglycerol catabolism is significant in myometrial tissue, thereby precluding its availability for the activation of protein kinase C. STUDY DESIGN: For these studies, uterine tissue was obtained from Sprague-Dawley rats both nonpregnant and with timed gestations. In vitro contraction studies were performed with cumulative additions of oxytocin (8-64 nmol/L) with and without R59022 (a diacylglycerol kinase inhibitor) or RHC80267 (a diacylglycerol lipase inhibitor). The contraction data were computer-digitalized, analyzed for total contractile activity, normalized for tissue cross-sectional area, and reported as the percentage of spontaneous activity. RESULTS: In myometrium from nonpregnant animals, inhibition of diacylglycerol lipase with RHC80267 had little effect on oxytocin-stimulated contractile activity, whereas inhibition of diacylglycerol kinase with R59022, although producing an increase in contractile frequency, markedly suppressed total oxytocin-stimulated contractile activity. In contrast, in myometrium from near-term pregnant animals both RHC80267 and R59022 produced marked suppression of oxytocin-stimulated contractile activity. CONCLUSIONS: These studies have demonstrated that prevention of diacylglycerol degradation, especially in response to inhibition of myometrial diacylglycerol kinase, results in the paradoxic oxytocin-mediated suppression of total myometrial contractile activity. These observations support the hypothesis that, when its catabolism is prevented, diacylglycerol produced in response to stimulation of the phosphatidylinositol-signaling pathway by oxytocin becomes available for protein kinase C activation, resulting in inhibition of myometrial contractile activity.
Authors:
J Ascher-Landsberg; T Saunders; M Phillippe
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  182     ISSN:  0002-9378     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-05     Completed Date:  2000-05-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  943-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Obstetrics and Gynecology, University of Chicago, IL 60637, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclohexanones / pharmacology
Diacylglycerol Kinase / antagonists & inhibitors
Diglycerides / physiology*
Enzyme Inhibitors / pharmacology
Female
Lipoprotein Lipase / antagonists & inhibitors
Myometrium / drug effects*,  physiology*
Oxytocin / pharmacology*
Pregnancy
Pregnancy, Animal / physiology*
Pyrimidinones / pharmacology
Rats
Rats, Sprague-Dawley
Reference Values
Thiazoles / pharmacology
Uterine Contraction / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
HD32449/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Cyclohexanones; 0/Diglycerides; 0/Enzyme Inhibitors; 0/Pyrimidinones; 0/Thiazoles; 50-56-6/Oxytocin; 83654-05-1/1,6-bis(cyclohexyloximinocarbonyl)hexane; 93076-89-2/R 59022; EC 2.7.1.107/Diacylglycerol Kinase; EC 3.1.1.34/Lipoprotein Lipase

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


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