ADENOSINE SELECTIVELY ATTENUATES H2-MEDIATED AND BETA-MEDIATED CARDIAC RESPONSES TO HISTAMINE AND NOREPINEPHRINE - AN UNMASKING OF H1-MEDIATED AND ALPHA-MEDIATED RESPONSES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 231  (2) , 215-223
Abstract
Adenosine is known to attenuate the positive inotropic and chronotropic effects of norepinephrine and histamine by reducing cAMP accumulation. This study assessed whether adenosine, while inhibiting the cardiac responses mediated by beta and H2 receptors, leaves unmodified the responses mediated by alpha and H1 receptors. In isolated cardiac preparations from the quinea pig, adenosine antagonized the positive inotropic effect of histamine more than that of norepinephrine. This most likely occurred because, by attenuating H2 and beta responses, adenosine unmasked the H1-negative and alpha-1-positive components of the inotropic effects of histamine and norepinephrine. The pure H2 agonist impromidine appeared to be antagonized by adenosine less than histamine, and norepinephrine less than isoproterenol. Adenosine antagonized the positive inotropic effect of norepinephrine in the presence of the alpha-1 blocker prazosin, whereas it did not affect the inotropic effect of phenylephrine. In the papillary muscle depolarized by 22 mM K+, adenosine antagonized the restoration of contractile responses induced by histamine or norepinephrine. This action of adenosine was reversed by the phosphodiesterase inhibitor papaverine and by the adenylate cyclase activator forskolin, suggesting that adenosine attenuates beta and H2 responses by suppressing the cAMP-dependent facilitation of Ca2+ influx promoted by the 2 amines. Data indicate that adenosine selectively attenuates H2 and beta but not alpha and H1 responses. When catecholamines, histamine and adenosine are released together as in myocardial ischemia, in addition to their individual effects, negative inotropism, decreased impulse conduction velocity and coronary constriction (i.e., H1-and alpha-mediated responses) may result from the adenosine-histamine-norepinephrine interaction.