Peptide and non-peptide opioid-induced hyperthermia in rabbits.
Intracerebroventricular administration of all three prototype non-peptide opioid receptor (mu, kappa and sigma) agonists, morphine, ketocyclazocine and N-allyl-normetazocine (SKF 10,047) induced hyperthermia in rabbits. Similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME) and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) also caused hyperthermia. As expected, the synthetic enkephalin DAME was more potent than the parent enkephalin. Of the three anion transport systems (iodide, hippurate and liver-like or L) present in the choroid plexus, it is suggested that only the L transport system seems to be important to ventricular inactivation of BE and DAME since iodipamide (an inhibitor of the L transport system) augmented the hyperthermia produced by BE and DAME. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide and non-peptide opioid-induced hyperthermia because a PG synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect on them. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine. BE, ME and DAME since naloxone attentuated them. In contrast, the hyperthermic response to ketocyclazocine and SKF 10,047 were not antagonized by naloxone.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004723:Endorphins / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D016314:Ethylketocyclazocine / Q000031:analogs & derivatives*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D001615:beta-Endorphin
D004723:Endorphins; D004745:Enkephalins; D010455:Peptides; D009270:Naloxone; D004744:Enkephalin, Methionine; D016314:Ethylketocyclazocine; D001615:beta-Endorphin; C013801:enkephalin-Met, Ala(2)-; C012395:ketazocine; C012134:SK&F 10047; D009020:Morphine; D010620:Phenazocine; D003496:Cyclazocine