Mu-, delta-, kappa- and epsilon-opioid receptor modulation of the hypothalamic-pituitary-adrenocortical (HPA) axis: subchronic tolerance studies of endogenous opioid peptides.
In opiate-naive rats, the endogenous opioid peptides, beta-endorphin, dynorphin(1-13) and Met-Enk-Arg-Phe (MEAP) and the synthetic enkephalin analogue D-Ala2-D-Leu5-Enk (DADLE) potently stimulated plasma corticosterone in a dose-dependent, naloxone reversible manner. To characterize their in vivo affinities, the effects of these peptides on plasma corticosterone release were tested in rats made tolerant to morphine, U50488H, DADLE/morphine or beta-endorphin. These cross-tolerance studies showed that dynorphin and MEAP exerted their action on plasma corticosterone release at kappa-opioid receptors. The action of DADLE occurred at delta-opioid receptors, while the action of beta-endorphin occurred principally at another receptor site. These results indicate that there is independent modulation of the hypothalamic-pituitary-adrenal axis by endogenous opioid peptides at mu-, delta- and kappa-opioid receptors. In addition there may be modulation by beta-endorphin at a separate site that we suggest could be a central epsilon-receptor site. This cross-tolerance paradigm, using a neuroendocrine model, provides in vivo evidence for the action of centrally active endogenous opioid peptides at multiple and independent opioid receptors.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D004361:Drug Tolerance; D004399:Dynorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin / Q000494:pharmacology*
D000700:Analgesics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C043460:epsilon receptor; D009270:Naloxone; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D016308:Enkephalin, Leucine-2-Alanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D009020:Morphine