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PubMed · 9205548

Adenosine A2 receptor function in rat ventricular myocytes.

J G Dobson·R A Fenton
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Abstract

OBJECTIVE: This study was undertaken to investigate the functional significance of adenosine A2 receptor stimulation in a mammalian ventricular myocyte preparation. METHODS: Isolated contracting rat ventricular myocytes were employed to assess the contractile, adenylyl cyclase and cyclic AMP responses to adenosine receptor stimulation. RESULTS: In single myocytes the presence of A1 receptors was confirmed, as indicated by the A1 receptor agonist, phenylisopropyladenosine (PIA), reducing by 60 and 74% the inotropic response and activation of adenylyl cyclase, respectively, elicited by the beta-adrenergic agonist, isoproterenol. An A1 receptor antagonist, dipropylcyclopentylxanthine (DPCPX), prevented the antiadrenergic action of PIA. The A2 receptor agonist, carboxyethylphenethyl-aminoethyl-carboxamido-adenosine (CGS-21680; 0.01-10 microM) increased myocyte inotropy in a concentration-dependent manner, reaching a maximum of 41-45%. Ethylcarboxamidoadenosine (NECA), naphthyl-substituted aralkoxy-adenosine (SHA-082) and adenosine in the presence of DPCPX also increased myocyte inotropy, as evidenced by increases in myocyte shortening, duration of shortening, time-to-peak shortening, time-to-75% relaxation and rate of maximal shortening. The agonists, however, did not effect the maximal rate of relaxation. The A2 receptor antagonists, chlorofuranyldihydrotri-azoloquinazolinimine (CGS-15943) and chlorostyrylcaffeine (CSC), the latter selective for the A2a receptor, prevented the contractile responses elicited by the A2 agonists. Compared to the concentrations of A2 receptor agonists necessary to increase myocyte contractile variables, 3-12 times greater concentrations of the agonist were required to increase myocyte adenylyl cyclase activity and cAMP levels. CONCLUSIONS: The results suggest the presence of adenosine A2a receptors in the rat ventricular myocyte that appear to be responsible for an increase in inotropy via cAMP-dependent and -independent mechanisms.

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AdenosineAdenosine-5'-(N-ethylcarboxamide)Adenylyl CyclasesAdrenergic beta-AgonistsAnimalsAntihypertensive AgentsCells, CulturedCyclic AMPHeart VentriclesIsoproterenolMyocardial ContractionMyocardiumPhenethylaminesPhenylisopropyladenosinePurinergic P1 Receptor AgonistsPurinergic P2 Receptor AgonistsRatsRats, Sprague-DawleyReceptors, Purinergic P2Stimulation, ChemicalVasodilator AgentsJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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BibTeXRIS

J G Dobson, R A Fenton. 1997. Adenosine A2 receptor function in rat ventricular myocytes.. https://doi.org/10.1016/s0008-6363(97)00023-0

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