Central effects of morphine and morphine-6-glucuronide on tissue
protein synthesis.
Hashiguchi, Yojiro, Patricia E. Molina, Victor R. Preedy, Peter H.
Sugden, Margaret A. McNurlan, Peter J. Garlick, and Naji N. Abumrad.
Departments of Surgery, Division of Surgical Research, SUNY at
Stony Brook, Stony Brook, NY 11794-8194; and Cardiac Medicine,
Cardiothoracic Institute, 2 Beaumont Street, London WIN 2DX, United
Kingdom
APStracts 3:0102R, 1996.
The central and peripheral effects of morphine sulfate (MOR) and
morphine-6-glucuronide (M6G) on the fractional rates of tissue
protein synthesis (ks) were determined. KS was determined in
conscious rats 2 h after intracerebroventricular (ICV) injection of
MOR (80 _g/rat), M6G (1 _g/rat) or water (H2O; 5 _l). ICV MOR and M6G
administration decreased kS in the liver (19%, 18%), spleen (19%,
17%), and gastrocnemius (18%, 17%) respectively. Intravenous (IV)
injection of MOR (8 mg/kg) or M6G (0.4 mg/kg) did not affect kS in
any of the tissues studied. ICV MOR and M6G resulted in an equivalent
10-15-fold increase in plasma epinephrine, 2-3-fold increase in
norepinephrine, and an 80-90 % increase in corticosterone, with no
change in insulin levels. ICV MOR produced a significant 30% decrease
in PaO2 and no significant changes in arterial pH and PaCO2 . ICV M6G
decreased PaO2 (40%), 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% oxygen (O2/N2 ; 1:19). One or 2 h hypoxia
decreased protein synthesis in the brain (47%, 56%), liver (69%,
69%), and skeletal muscle (51%, 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.
Received 13 October 1995; accepted in final form 28 February
1996.
APS Manuscript Number R649-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 27 March 96