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 cathete rized conscious rats received an intracerebroventricular injection of[ D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAGO, 0.5, 2, or 8 nmol/rat ) or water (5 mu l) 45 min before determination of protein synthesis b y 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 O-2 pressure 44.2 +/- 3.4 Torr, arteria l O-2 saturation 65.3 +/- 5.5%, and PCO2 66.3 +/- 4.4; Torr). Intracer ebroventricular DAGO increased circulating levels of catecholamines, c orticosterone, and growth hormone but did not alter those of insulin a nd insulin-like growth factor I. Significant positive correlations bet ween protein synthesis and pH were observed in the tissues studied (i. e., liver protein synthesis vs. pH, P < 0.0001, r = 0.902; gastrocnemi us protein synthesis vs. pH, P < 0.0001, r = 0.830). Our results indic ate that mu-receptor stimulation inhibits tissue protein synthesis, an d this effect appears to be secondary to respiratory depression and th e resulting acidosis and/or hypoxia. Furthermore, our findings suggest differential sensitivity in tissue response to alterations in pH, hyp oxia, and stress hormone elevation.