AJP - Regulatory, Integrative and Comparative Physiology, Vol 271, Issue 3 619-R625, Copyright © 1996 by American Physiological Society
Central effects of morphine and morphine-6-glucuronide on tissue protein synthesis
Y. Hashiguchi, P. E. Molina, V. R. Preedy, P. H. Sugden, M. A. McNurlan, P. J. Garlick and N. N. Abumrad
Department of Surgery, State University of New York at Stony Brook 11794-8194, USA.
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.
