Central effects of morphine and morphine-6-glucuronide on tissue protein synthesis

Abstract

The central and peripheral effects of morphine sulfate (Mor) and morphine-6-glucuronide (M6G) on the fractional rates of tissue protein synthesis (kappa s) were determined. We determined ks in conscious rats 2 h after intracerebroventricular injection of Mor (80 micrograms/rat), M6G (1 microgram/rat), or H2O (5 microliters). Intracerebroventricular Mor and M6G administration decreased ks in the liver by 19 and 18% spleen by 19 and 17%, and gastrocnemius by 18 and 17%, respectively. Intravenous injection of Mor (8 mg/kg) or M6G (0.4 mg/kg) did not affect ks in any of the tissues studied. Intracerebroventricular Mor and M6G resulted in an equivalent 10- to 15-fold increase in plasma epinephrine, 2- to 3-fold increase in norepinephrine, and 80-90% increase in corticosterone, with no change in insulin levels. Intracerebroventricular Mor produced a significant 30% decrease in arterial partial O2 pressure (PaO2) and no significant changes in arterial pH and arterial partial CO2 pressure (PacO2). Intracerebroventricular M6G decreased PaO2 (40%) and pH (from 7.44 +/- 0.01 to 7.34 +/- 0.02) and increased Paco2 (36%). The potential contribution of hypoxia to the opiate-induced decrease in ks was assessed in an additional set of rats exposed to 5% O2-95% N2. One or 2 h of hypoxia decreased protein synthesis in the brain by 47 and 56%, liver by 69 and 69%, and skeletal muscle by 51 and 52%, respectively. Our results indicate that Mor and M6G suppress tissue protein synthesis through central mechanisms, most likely mediated by opiate-induced respiratory depression in association with neural and hormonal alterations.