mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides.
Four experiments were done to determine which receptor type(s) mediates the effects of third ventricular microinjections of four opioid peptide agonists on blood levels of glucose, free fatty acids, and corticosterone. Tests were performed in unanesthetized adult male albino rats having chronic intraventricular cannulas; blood samples were taken from the tail tip at 0, 15, 30, 60, 90, and 120 min postmicroinjection. In experiment 1, the agonists DAGO (Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol), beta-endorphin, DSLET (d-Ser2-Leu-enkephalin-Thr), and dynorphin A-(1-17) (0, 0.3, 1, 3, and 10 nmol/rat) produced three distinct patterns of changes in serum glucose, free fatty acid, and corticosterone values. Experiment 2 showed that the effects of DAGO and beta-endorphin were inhibited by prior injection with the opiate-receptor blocker naloxone (1 mg/kg sc) and that the effects of dynorphin were not diminished. Experiment 3 determined that dynorphin effects were also not diminished by naloxone given intraventricularly. Experiment 4 found that blockade of the mu-receptor by intraventricular pretreatment with the specific antagonist beta-funaltrexamine (20 micrograms/rat, 24 h before) completely abolished the effects of DAGO and beta-endorphin on glucose and corticosterone. The mu-receptor is critical to the mediation of the hyperglycemia and hypercorticosteronemia induced by the central administration of opiate agonists. These results imply that mu-opioid binding sites previously identified in central autonomic regions may be involved in the regulation of circulating glucose and corticosterone.
Geriatric Research, Education, and Clinical Center, Sepulveda Veterans Affairs Medical Center, California 91343.
M W
MW
Gunion
M J
MJ
Rosenthal
J E
JE
Morley
S
S
Miller
B
B
Zib
B
B
Butler
R D
RD
Moore
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000502:physiology*; D003345:Corticosterone / Q000097:blood*; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007276:Injections, Intraventricular; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin / Q000494:pharmacology
D001786:Blood Glucose; D004745:Enkephalins; D005230:Fatty Acids, Nonesterified; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D001615:beta-Endorphin; C024524:beta-funaltrexamine; D004399:Dynorphins; D003345:Corticosterone