CENTRAL EFFECTS OF MORPHINE AND MORPHINE-6-GLUCURONIDE ON TISSUE PROTEIN-SYNTHESIS

The central and peripheral effects of morphine sulfate (Mor) and morph ine-6-glucuronide (M6G) on the fractional rates of tissue protein synt hesis (k(s)) were determined. We determined k(s) in conscious rats 2 h after intracerebroventricular injection of Mor (80 mu g/rat), M6G (1 mu g/rat), or H2O (5 mu l). Intracerebroventricular Mor and M6G admini stration decreased h, 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 k(s) in any of the tissues studied. Intracerebroventricular Mor and M6G resulted in an e quivalent 10- to 15-fold increase in plasma epinephrine, 2- to 3-fold increase in norepinephrine, and 80-90% increase in corticosterone, wit h no change in insulin levels. Intracerebroventricular Mor produced a significant 30% decrease in arterial partial O-2 pressure (Pa-O2) and no significant changes in arterial pH and arterial partial CO2 pressur e (Pa-CO2). Intracerebroventricular M6G decreased Pa-O2 (40%) and pH ( from 7.44+/-0.01 to 7.34+/-0.02) and increased Pa-CO2 (36%). The poten tial contribution of hypoxia to the opiate;induced decrease in h, was assessed in an additional set of rats exposed to 5% O-2-95% N-2. One o r 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%, respectivel y. Our results indicate that Mor and M6G suppress tissue protein synth esis through central mechanisms, most likely mediated by opiate-induce d respiratory depression in association with neural and hormonal alter ations.