Document Detail

Effects of carbachol and (-)-N6-phenylisopropyladenosine on myocardial inositol phosphate content and force of contraction.
MedLine Citation:
PMID:  2085707     Owner:  NLM     Status:  MEDLINE    
1. The effects of carbachol and the A1-adenosine receptor agonist (-)-N6-phenylisopropyladenosine (PIA) on force of contraction and inositol lipid metabolism were studied in electrically driven left auricles and papillary muscles isolated from guinea-pig hearts. Both carbachol and PIA (0.01-10 microM) had concentration-dependent negative inotropic effects in auricles. In papillary muscles PIA had no inotropic effect. Carbachol also had no inotropic effect at low concentrations (0.01-1 microM) but at 10-100 microM it exerted a slight positive inotropic effect. 2. In auricles and papillary muscles both carbachol and PIA concentration-dependently increased inositol trisphosphate (IP3; significant at 1 microM). Accordingly phosphatidylinositol bisphosphate (PIP2), the precursor of IP3, was reduced. All effects of carbachol and PIA were antagonized by atropine (10 microM) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 20 microM) respectively, indicating receptor-mediated effects. 3. In auricles the negative inotropic effects of carbachol and PIA preceded the increase in IP3. 4. In papillary muscles the increase in IP3 preceded the slight positive inotropic effect of carbachol, indicating that the M-cholinoceptor-mediated increase in IP3 and force of contraction may be related. However, PIA showed a comparable increase in IP3 but no inotropic effect, indicating a dissociation between those parameters. 5. In conclusion, in previous studies a close relation between increases in IP3 and force of contraction has been shown after alpha 1-adrenoceptor stimulation. The present study with carbachol supports this view. However, the present data for PIA could not show such a close relationship, questioning the role of IP3 as an endogenous regulator of force of contraction.
C Kohl; B Linck; W Schmitz; H Scholz; J Scholz; M Tóth
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  101     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1990 Dec 
Date Detail:
Created Date:  1991-05-23     Completed Date:  1991-05-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  829-34     Citation Subset:  IM    
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, FRG.
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MeSH Terms
Carbachol / pharmacology*
Electric Stimulation
Guinea Pigs
Heart / drug effects
Inositol Phosphates / metabolism*
Myocardial Contraction / drug effects*
Myocardium / metabolism*
Papillary Muscles / drug effects,  metabolism
Phenylisopropyladenosine / pharmacology*
Xanthines / pharmacology
Reg. No./Substance:
0/Inositol Phosphates; 0/Xanthines; 102146-07-6/1,3-dipropyl-8-cyclopentylxanthine; 29193-86-0/Phenylisopropyladenosine; 51-83-2/Carbachol

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