Related Experiment Videos
Central opiate mu-receptor-mediated suppression of tissue protein synthesis
Y Hashiguchi1, P E Molina, S Dorton
1Department of Surgery, North Shore University Hospital, Manhasset 11030, USA.
Abstract:
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.
Insights
Central mu-opioid receptor stimulation with DAGO significantly decreases tissue protein synthesis, particularly in organs like the liver and kidney. This effect is linked to respiratory depression, acidosis, and hypoxia, not direct receptor action.
Area of Science:
- Neuropharmacology
- Physiology
- Biochemistry
Background:
- Mu-opioid receptor agonists are used clinically, but their systemic effects on protein synthesis are not fully understood.
- Central administration allows targeted receptor activation, minimizing peripheral side effects.
Purpose of the Study:
- To investigate the dose-dependent effects of central mu-opioid receptor stimulation on tissue protein synthesis rates.
- To determine if observed effects are secondary to respiratory depression and associated physiological changes.
Main Methods:
- Conscious rats received intracerebroventricular injections of [D-Ala2, N-Me-Phe4,Gly5-ol]enkephalin (DAGO) or vehicle.
- Protein synthesis was measured using the flooding dose technique.
- Arterial blood gases, hormone levels, and catecholamines were analyzed.
Main Results:
- DAGO significantly decreased protein synthesis in liver, spleen, gut, kidney, and certain muscles, but not brain, heart, or soleus.
- DAGO induced dose-dependent respiratory depression, leading to acidosis, hypoxia, and hypercapnia.
- Circulating catecholamines, corticosterone, and growth hormone increased, while insulin and IGF-I remained unchanged.
- Positive correlations were found between tissue protein synthesis and pH.
Conclusions:
- Central mu-opioid receptor stimulation inhibits tissue protein synthesis, primarily as a consequence of respiratory depression and resultant acidosis/hypoxia.
- Different tissues exhibit varying sensitivity to these physiological disturbances.
- The findings highlight the complex interplay between opioid signaling, respiratory function, and metabolic processes.