The indirect negative inotropic effects of the P1-receptor agonist, L-phenylisopropyladenosine, in guinea-pig isolated cardiac preparations: comparison with cromakalim.

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  • Author(s): Urquhart RA;Urquhart RA; Broadley KJ
  • Source:
    Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 1992 Jun; Vol. 70 (6), pp. 910-5.
  • Publication Type:
    Comparative Study; Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Canadian Science Publishing Country of Publication: Canada NLM ID: 0372712 Publication Model: Print Cited Medium: Print ISSN: 0008-4212 (Print) Linking ISSN: 00084212 NLM ISO Abbreviation: Can J Physiol Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: 2011- : Ottawa, ON : Canadian Science Publishing
      Original Publication: Ottawa, National Research Council of Canada.
    • Subject Terms:
      Benzopyrans/*pharmacology ; Myocardial Contraction/*drug effects ; Phenylisopropyladenosine/*pharmacology ; Pyrroles/*pharmacology; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology ; Animals ; Atrial Function ; Atrial Function, Left/drug effects ; Cardiotonic Agents/pharmacology ; Colforsin/pharmacology ; Cromakalim ; Depression, Chemical ; Guinea Pigs ; Heart Atria/drug effects ; In Vitro Techniques ; Isoproterenol/pharmacology ; Male ; Papillary Muscles/drug effects ; Papillary Muscles/physiology ; Stimulation, Chemical ; Time Factors
    • Abstract:
      The possible mechanisms of the indirect negative inotropic responses to the P1-receptor agonist, L-phenylisopropyladenosine (L-PIA) were evaluated in electrically paced (2 Hz, 5 ms pulse width, voltage 50% above threshold) left atria and papillary muscles of guinea pigs. The responses were compared in naive tissues (direct effects) or after prestimulation with submaximal concentrations of either cAMP-dependent positive inotropes (isoprenaline or forskolin) or the cAMP-independent inotrope Bay K 8644. Cumulative concentration-response curves were obtained in naive or prestimulated preparations for L-PIA or the potassium channel activator, cromakalim, for comparison. L-PIA and cromakalim exerted negative inotropy in naive atrial tissues, whereas only cromakalim was active in naive papillary muscles. In atria prestimulated with isoprenaline (31 nM) or forskolin (1.4 microM), the negative inotropy of L-PIA was enhanced compared with naive tissues. In contrast, prestimulation with Bay K 8644 (1 microM) exerted a significant functional antagonism of the response to L-PIA. In the case of cromakalim, prestimulation with isoprenaline exerted a functional antagonistic effect. In papillary muscles, an indirect negative inotropic effect of L-PIA was only seen in tissues prestimulated with the cAMP-dependent inotropes isoprenaline (31 nM) or forskolin (2.4 microM), and not in naive tissues or those prestimulated by Bay K 8644 (333 nM). As with atria, prestimulation with isoprenaline exerted a functional antagonistic effect on the response to cromakalim. These results suggest that the P1-receptor agonist, L-PIA, exerts its indirect negative inotropic effects in left atria by two mechanisms.2+ with cAMP-dependent positive inotropes.(ABSTRACT TRUNCATED AT 250 WORDS)
    • Accession Number:
      0 (Benzopyrans)
      0 (Cardiotonic Agents)
      0 (Pyrroles)
      0G4X367WA3 (Cromakalim)
      1F7A44V6OU (Colforsin)
      29193-86-0 (Phenylisopropyladenosine)
      71145-03-4 (3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester)
      L628TT009W (Isoproterenol)
    • Publication Date:
      Date Created: 19920601 Date Completed: 19921223 Latest Revision: 20190720
    • Publication Date:
      20250114
    • Accession Number:
      10.1139/y92-122
    • Accession Number:
      1384946