DIFFERENTIAL COUPLING OF ALPHA(1)-ADRENORECEPTOR SUBTYPES TO PHOSPHOLIPASE-C AND MITOGEN-ACTIVATED PROTEIN-KINASE IN NEONATAL RAT CARDIAC MYOCYTES

Activation of cardiac alpha(1)-adrenoreceptors has a number of physiol ogical effects. Ascribing these effects to a specific alpha(1)-adrenor eceptor subtype first requires the elucidation of the subtypes that ar e present in the tissue of interest. In the present study, mRNA transc ripts for the alpha(1A), alpha(1B), and alpha(1D)-adrenoreceptor subty pes were detected in cultured neonatal rat cardiac myocytes, using rev erse transcriptase-polymerase chain reaction analysis. However, bindin g sites for only the alpha(1A) and alpha(1B)-adrenoreceptor subtypes w ere detected in cultured neonatal rat cardiac myocytes, using competit ion binding analysis with a variety of alpha(1) selective receptor ant agonists. Phenylephrine-stimulated phosphatidylinositol hydrolysis was inhibited by alpha(1) selective receptor antagonists with affinities consistent with the alpha(1A)-adrenoreceptor subtype, whereas phenylep hrine-induced activation of the mitogen activated protein kinase casca de was inhibited by these same antagonists with affinities more closel y resembling the alpha(1B)-adrenoreceptor subtype. In the case of both signaling pathways, alpha(1D) selective receptor antagonist, BMY 7378 , exhibited affinities suggestive of the relative absence of alpha(1D) -adrenoreceptor subtype. Thus, despite the presence of mRNA transcript s for all three alpha(1)-adrenoreceptor subtypes, only the alpha(1A) a nd alpha(1B)-adrenoreceptor subtypes were expressed and functionally c oupled at detectable levels in neonatal rat cardiac myocytes. Of parti cular interest, phenylephrine-induced activation of the mitogen activa ted protein kinase cascade appears to be mediated by a subtype resembl ing most closely the pharmacological profile of the alpha(1B)-adrenore ceptor subtype. (C) 1997 Elsevier Science B.V.