Etorphine inhibition of pancreatic exocrine secretion in rats: comparison with methadone.
The effects of etorphine, a potent opiate agonist without preferential affinity for mu, delta or kappa receptors, on exocrine pancreatic secretion were studied in rats fitted with chronic or acute pancreatic fistulas and compared to those of methadone, a well-documented mu agonist. In conscious rats etorphine (3 micrograms/kg s.c.) inhibited basal pancreatic secretion by about 50% for volume and bicarbonate output and by 70% for protein output. Pancreatic secretion returned to its basal level within 2 h. Methadone (5 mg/kg s.c.) was about equipotent but the inhibition lasted longer. The effects of both etorphine and methadone were completely antagonized by naloxone (1 mg/kg s.c.) and to a lesser extent by diprenorphine (10 microgram/kg s.c.). Yohimbine did not suppress the inhibitory effect of etorphine on protein output but showed some antagonism against the effects of etorphine on water and bicarbonate output. In anaesthetized rats etorphine (3 micrograms/kg) inhibited the pancreatic secretion stimulated by 2-deoxy glucose, a centrally acting vagal stimulatory agent, by 50-60% for volume and bicarbonate output and totally for protein output. The same dose of etorphine did not inhibit the pancreatic secretion evoked by vagal electrical stimulation, a peripheral stimulus. Methadone (5 mg/kg) inhibited the pancreatic secretion stimulated by 2-deoxy glucose to the same extent, but for a longer time than etorphine, and at the same dose did not suppress the pancreatic pancreatic response to vagal electrical stimulation. The inhibitory effects of etorphine and methadone in anaesthetized rats were completely suppressed by naloxone (1 mg/kg s.c.) and only reduced by diprenorphine (10 micrograms/kg s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)
D000758:Anesthesia; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D004174:Diprenorphine / Q000494:pharmacology; D004558:Electric Stimulation; D005048:Etorphine / Q000494:pharmacology*; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D009019:Morphinans / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology
D009019:Morphinans; D004174:Diprenorphine; D009270:Naloxone; D005048:Etorphine; D003847:Deoxyglucose; D008691:Methadone