Expression of a1-adrenergic receptor subtypes in heart cell culture

Original Abstract: Three a sub(1)AR subtypes have been cloned so far and are designated as a sub(1a), a sub(1b), and a sub(1d). Organspecific distribution pattern and subtype-specific effects are known but not fully understood. To address a cell-type specific expression pattern in the heart we investigated expression pattern of a sub(1)AR subtypes on RNA and proteinlevel in heart tissue, cultured cardiomyocytes and nonmyocytes of the rat. Each a sub(1)ARsubtype mRNA was present in neonatal and adult rat heart culture but the relative distribution pattern was significantly different. While the a sub(1a)AR subtype is preferentially expressed in adult cardiomyocytes, the a sub(1b)AR subtype was preferentially expressed in the nonmyocyte cell fraction. The RTPCR results were confirmed by Westernblotting (a sub(1b)) and immunocytochemical studies. Incubation with an a sub(1)agonist (phenylephrine) for 72 h led to a significant reduction of the a sub(1b)AR in neonatal heart cell culture on both mRNA and protein level. In contrast, incubation with an a sub(1)antagonist (prazosin) induced a 1.6 fold upregulation of the a sub(1a)AR mRNA without significant effects on radioligand binding and functional assay. The results indicate a distribution pattern of the a sub(1)AR subtype which is specific for cell type and ontogeny of the rat heart and may be regulated by adrenergic agents.