Differential coupling of α1-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 physiological effects. Ascribing these effects to a specific alpha(1)-adrenoreceptor subtype first requires the elucidation of the subtypes that are present in the tissue of interest. In the present study, mRNA transcripts for the alpha(1A), alpha(1B), and alpha(1D)-adrenoreceptor subtypes were detected in cultured neonatal rat cardiac myocytes, using reverse transcriptase-polymerase chain reaction analysis. However, binding sites for only the alpha(1A) and alpha(1B)-adrenoreceptor subtypes were detected in cultured neonatal rat cardiac myocytes, using competition binding analysis with a variety of alpha(1) selective receptor antagonists. Phenylephrine-stimulated phosphatidylinositol hydrolysis was inhibited by alpha(1) selective receptor antagonists with affinities consistent with the alpha(1A)-adrenoreceptor subtype, whereas phenylephrine-induced activation of the mitogen activated protein kinase cascade was inhibited by these same antagonists with affinities more closely 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 transcripts for all three alpha(1)-adrenoreceptor subtypes, only the alpha(1A) and alpha(1B)-adrenoreceptor subtypes were expressed and functionally coupled at detectable levels in neonatal rat cardiac myocytes. Of particular interest, phenylephrine-induced activation of the mitogen activated protein kinase cascade appears to be mediated by a subtype resembling most closely the pharmacological profile of the alpha(1B)-adrenoreceptor subtype. (C) 1997 Elsevier Science B.V.