α-adrenergic stimulation of respiration in isolated rat hepatocytes

Abstract

The .alpha.-adrenergic agonists noradrenaline [norepinephrine] (in the presence of .beta.-blocker) and phenylephrine cause a transient stimulation of the respiration in isolated rat hepatocytes. After a lag period of 12 s, this activation 1st attains its maximal value (+ 24%) for .apprx. 1 min and then falls to a sustained vlue (+ 15%). The effect is blocked by the .alpha.-antagonists phenoxybenzamine and phentolamine. It is dose-dependent, with a half-maximal stimulation by 16 nM-noradrenaline, which is similar to that found for other cell responses to the hormone. Vasopressin and ATP, which in common with .alpha.-agonists are believed to increase intracellular [Ca2+], induce similar activation in the respiration rate. The .alpha.-adrenergic-mediated respiration depends on extracellular Ca2+. The activation is decreased or abolished when extracellular [Ca2+] is decreased by adding EGTA [ethylene glycol bis (.beta.-aminoethylether)-N,N''-tetraacetic acid], or when the Ca2+ antagonists Mn2+ and La3+ are present in the incubation medium. The activation of the mitochondrial respiration rate probably results from the increase in cytosolic Ca2+ concentration, presumably via Ca2+ influx or Ca2+ release from the plasma membrane or endoplasmic reticulum.