Central opiate mu-receptor-mediated suppression of tissue protein synthesis.
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.
Hashiguchi
Y
Y
Department of Surgery, North Shore University Hospital, Manhasset 11030, USA.
Molina
P E
PE
Dorton
S
S
McNurlan
M A
MA
Garlick
P J
PJ
Reddy
D
D
Abumrad
N N
NN
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D002245:Carbon Dioxide / Q000097:blood; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003903:Deuterium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007276:Injections, Intraventricular; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D010100:Oxygen / Q000097:blood; D010108:Oxyhemoglobins / Q000378:metabolism; D010313:Partial Pressure; D010649:Phenylalanine / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000502:physiology*; D012044:Regression Analysis; D012119:Respiration / Q000187:drug effects; D013154:Spleen / Q000378:metabolism
D001639:Bicarbonates; D004745:Enkephalins; D010108:Oxyhemoglobins; D017450:Receptors, Opioid, mu; D010725:Phosphocreatine; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002245:Carbon Dioxide; D010649:Phenylalanine; D000255:Adenosine Triphosphate; D003903:Deuterium; D010100:Oxygen