β-Adrenergic potentiation of endoplasmic reticulum Ca2+ release in brown fat cells

Abstract

We find that the adrenergic agonist isoproterenol increases intracellular Ca2+ concentration ([Ca2+]i) in cultured rat brown adipocytes. At the concentration used (10 μM), isoproterenol-induced Ca2+ responses were sensitive to block by either α1- or β-adrenergic antagonists, suggesting an interaction between these receptor subtypes. Despite reliance on β-adrenoceptor activation, the Ca2+ response was not due solely to increases in cAMP because, administered alone, the selective β3-adrenergic agonist BRL-37344 or forskolin did not increase [Ca2+]i. However, increased cAMP elicited vigorous [Ca2+]i increases in the presence of barely active concentrations of the α-adrenergic agonist phenylephrine or the P2Y receptor agonist UTP. Consistent with isoproterenol recruiting only inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores, endoplasmic reticulum store depletion by thapsigargin blocked isoproterenol-induced Ca2+ increases, but removal of external Ca2+did not. These results argue that increases in cAMP sensitize the IP3-mediated Ca2+ release system in brown adipocytes.