α1-adrenergic stimulation mediates Ca2+-dependent inositol phosphate formation through the α1B-like adrenoceptor subtype in adult rat cardiac myocytes

✍ Scribed by Stelios Seraskeris; Antigone Lazou

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 184 KB
• Volume: 84
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.1281

✦ Synopsis

Abstract

We studied the effects of increased Ca^2+^ influx on α~1~‐adrenoceptor‐stimulated InsP formation in adult rat cardiac myocytes. We further examined if such effects could be mediated through a specific α~1~‐adrenoceptor subtype. [^3^H]InsP responses to adrenaline were dependent on extracellular Ca^2+^ concentration, from 0.1 μM to 2 mM, and were completely blocked by Ca^2+^ removal. However, in cardiac myocytes preloaded with BAPTA, a highly selective calcium chelating agent, Ca^2+^ concentrations higher than 1 μM had no effect on adrenaline‐stimulated [^3^H]InsP formation. Taken together these results suggest that [^3^H]InsP formation induced by α~1~‐adrenergic stimulation is in part mediated by increased Ca^2+^ influx. Consistent with this, ionomycin, a calcium ionophore, stimulated [^3^H]InsP formation. This response was additive with the response to adrenaline stimulation implying that different signaling mechanisms may be involved. In cardiac myocytes treated with the α~1B~‐adrenoceptor alkylating agent, CEC, [^3^H]InsP formation remained unaffected by increased Ca^2+^ concentrations, a pattern similar to that observed when intracellular Ca^2+^ was chelated with BAPTA. In contrast, addition of the α~1A~‐subtype antagonist, 5′‐methyl urapidil, did not affect the Ca^2+^ dependence of [^3^H]InsP formation. Neither nifedipine, a voltage‐dependent Ca^2+^ channel blocker nor the inorganic Ca^2+^ channel blockers, Ni^2+^ and Co^2+^, had any effect on adrenaline stimulated [^3^H]InsP, at concentrations that inhibit Ca^2+^ channels. The results suggest that in adult rat cardiac myocytes, in addition to G protein‐mediated response, α~1~‐adrenergic‐stimulated [^3^H]InsP formation is activated by increased Ca^2+^ influx mediated by the α~1B~‐subtype. J. Cell. Biochem. 84: 201–210, 2002. © 2001 Wiley‐Liss, Inc.