Adrenoceptor desensitization after immobilization stress or repeated injection of isoproterenol

Immobilization stress (2.5 h daily) or repeated injection of isoproterenol (1 mg/kg, 3 times daily) for 1 wk caused a subsensitivity to the chronotropic and pressor effect of epinephrine in pithed rats. Propranolol (1 mg/kg) inhibited, to a greater extent in control than in immobilized rats, the chronotropic effect of epinephrine. The residual heart rates did not differ significantly among control, immobilized, and isoproterenol-treated rats. Practolol (1 mg/kg) but not butoxamine (5 mg/kg) mimicked the effect of propranolol. The subsensitivity in the blood pressure responses was not abolished by injection of either of the beta-adrenoceptor blockers. Butoxamine or propranolol shifted the epinephrine dose-blood pressure response curves to the left. The degree of shift was similar in control and immobilized or isoproterenol-treated rats. Daily injection of quinacrine (16 mg/kg), an antimalarial agent that inhibits phospholipase A2, blocked the subsensitivity to the chronotropic effect of epinephrine, but not that to the pressor effect of epinephrine. These observations suggest that immobilization stress causes desensitization of alpha- and beta 1-receptors but not beta 2-receptors. The mechanism of desensitization of beta 1-receptors by immobilization appears to be similar to that after isoproterenol treatment, possibly due to increased turnover of phospholipids.