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

1996 ◽  
Vol 271 (3) ◽  
pp. R619-R625 ◽  
Author(s):  
Y. Hashiguchi ◽  
P. E. Molina ◽  
V. R. Preedy ◽  
P. H. Sugden ◽  
M. A. McNurlan ◽  
...  

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.

1997 ◽  
Vol 273 (3) ◽  
pp. R920-R927 ◽  
Author(s):  
Y. Hashiguchi ◽  
P. E. Molina ◽  
S. Dorton ◽  
M. A. McNurlan ◽  
P. J. Garlick ◽  
...  

We determined the dose-dependent effects of central mu-opioid receptor stimulation on rates of tissue protein synthesis. Chronically catheterized conscious rats received an intracerebroventricular injection of [D-Ala2, N-Me-Phe4,Gly5-ol]enkephalin (DAGO, 0.5, 2, or 8 nmol/rat) or water (5 microliters) 45 min before determination of protein synthesis by the flooding dose technique. DAGO produced a significant decrease in tissue protein synthesis in liver (57%), spleen (54%), gut mucosa (36%), gut serosa (23%), kidney (48%), gastrocnemius (33%), and plantaris muscle (27%), but it did not alter rates of protein synthesis in the brain, heart, and soleus muscle. DAGO produced an acute dose-dependent respiratory depression 30 min after intracerebroventricular injection; this depression resulted in acidosis, hypoxia, and hypercapnia (pH 7.19 +/- 0.04, arterial partial O2, pressure 44.2 +/- 3.4 Torr, arterial O2 saturation 65.3 +/- 5.5%, and PCO2 66.3 +/- 4.4 Torr). Intracerebroventricular DAGO increased circulating levels of catecholamines, corticosterone, and growth hormone but did not alter those of insulin and insulin-like growth factor I. Significant positive correlations between protein synthesis and pH were observed in the tissues studied (i.e., liver protein synthesis vs. pH, P < 0.0001, r = 0.902; gastrocnemius protein synthesis vs. pH, P < 0.0001, r = 0.830). Our results indicate that mu-receptor stimulation inhibits tissue protein synthesis, and this effect appears to be secondary to respiratory depression and the resulting acidosis and/or hypoxia. Furthermore, our findings suggest differential sensitivity in tissue response to alterations in pH, hypoxia, and stress hormone elevation.


1988 ◽  
Vol 61 (5) ◽  
pp. 429-441 ◽  
Author(s):  
D. N. McMillan ◽  
D. F. Houlihan

2012 ◽  
Vol 58 (4) ◽  
pp. 297-302 ◽  
Author(s):  
Kazuyo TUJIOKA ◽  
Takashi YAMADA ◽  
Mami AOKI ◽  
Koji MORISHITA ◽  
Kazutoshi HAYASE ◽  
...  

2006 ◽  
Vol 165 (3) ◽  
pp. 297-311 ◽  
Author(s):  
S DANICKE ◽  
T GOYARTS ◽  
S DOLL ◽  
N GROVE ◽  
M SPOLDERS ◽  
...  

1990 ◽  
Vol 120 (9) ◽  
pp. 1006-1015 ◽  
Author(s):  
Claude Champredon ◽  
Elisabeth Debras ◽  
Philippe Patureau Mirand ◽  
Maurice Arnal

2002 ◽  
Vol 283 (4) ◽  
pp. E638-E647 ◽  
Author(s):  
Teresa A. Davis ◽  
Marta L. Fiorotto ◽  
Douglas G. Burrin ◽  
Rhonda C. Vann ◽  
Peter J. Reeds ◽  
...  

Studies have shown that protein synthesis in skeletal muscle of neonatal pigs is uniquely sensitive to a physiological rise in both insulin and amino acids. Protein synthesis in cardiac muscle, skin, and spleen is responsive to insulin but not amino acid stimulation, whereas in the liver, protein synthesis responds to amino acids but not insulin. To determine the response of protein synthesis to insulin-like growth factor I (IGF-I) in this model, overnight-fasted 7- and 26-day-old pigs were infused with IGF-I (0, 20, or 50 μg · kg−1 · h−1) to achieve levels within the physiological range, while amino acids and glucose were clamped at fasting levels. Because IGF-I infusion lowers circulating insulin levels, an additional group of high-dose IGF-I-infused pigs was also provided replacement insulin (10 ng · kg−0.66 · min−1). Tissue protein synthesis was measured using a flooding dose ofl-[4-3H]phenylalanine. In 7-day-old pigs, low-dose IGF-I increased protein synthesis by 25–60% in various skeletal muscles as well as in cardiac muscle (+38%), skin (+24%), and spleen (+32%). The higher dose of IGF-I elicited no further increase in protein synthesis above that found with the low IGF-I dose. Insulin replacement did not alter the response of protein synthesis to IGF-I in any tissue. The IGF-I-induced increases in tissue protein synthesis decreased with development. IGF-I infusion, with or without insulin replacement, had no effect on protein synthesis in liver, jejunum, pancreas, or kidney. Thus the magnitude, tissue specificity, and developmental change in the response of protein synthesis to acute physiological increases in plasma IGF-I are similar to those previously observed for insulin. This study provides in vivo data indicating that circulating IGF-I and insulin act on the same signaling components to stimulate protein synthesis and that this response is highly sensitive to stimulation in skeletal muscle of the neonate.


1992 ◽  
Vol 70 (11) ◽  
pp. 2095-2102 ◽  
Author(s):  
A. R. Foster ◽  
D. F. Houlihan ◽  
S. J. Hall ◽  
L. J. Burren

Juvenile cod were acclimated to cold (5 °C) and warm (15 °C) water temperatures and fed sandeel at a similar ration size (3% body weight∙day−1) for at least 40 days. After this acclimation period, there were no significant differences in either weight-specific growth rate or weight-specific tissue protein synthesis rates (ventricle, gill, stomach, and intestine) between the cold- and warm-acclimated fish. However, every cold-acclimated tissue examined had a significantly higher RNA concentration (μg RNA∙g tissue−1) than the respective warm-acclimated tissue. Cold-acclimated ventricle and intestine had significantly reduced RNA activities (i.e., translational efficiency, g protein synthesized∙g RNA−1∙day−1) compared with the warm-acclimated tissues. In contrast, the mean RNA activities of cold-acclimated stomach and gill were not significantly different from those of the same tissues in the warm-acclimated fish. These alterations in RNA activity and RNA concentration with temperature acclimation probably represent a thermal compensatory mechanism for protein synthesis and growth in cod at 5 °C. Positive linear relationships were observed between tissue protein synthesis rates and tissue RNA concentrations (μg RNA∙g tissue−1). RNA/protein ratios (μg RNA∙mg protein−1) gave a positive (but statistically insignificant) trend with protein synthesis rates. In contrast, a negative trend (statistically insignificant) was observed between tissue protein synthesis rates and tissue RNA/DNA ratios (μg RNA∙μg DNA−1). The use of RNA measurements as biochemical correlates of growth rate in juvenile cod is discussed.


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