Hyperthermic responses to central injections of some peptide and non-peptide opioids in the guinea-pig.
Intracerebroventricular administration of prototype non-peptide opioid receptor (mu, kappa, sigma) agonists, morphine, ketocyclazocine and N-allyl normetazocine (SKF 10,047) and an agonist at both kappa and sigma receptors, pentazocine, induced hyperthermia in guinea-pigs. Similar administration of peptide opioids like beta-endorphin (BE), methionine enkephalin (Met-E), leucine enkephalin (Leu-E) and their synthetic analogues D-ala2-methionine-enkephalinamide (D-ala2-Met-E) and D-ala2-leucine-enkephalinamide (D-ala2-Leu-E) also caused hyperthermia. Of the three anion transport systems (iodide, hippurate and liver-like) present in the choroid plexus, only the liver-like transport system seems to be important to central inactivation of beta-endorphin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin since iodipamide (an inhibitor of the liver-like transport system) augmented the hyperthermia. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide- and non-peptide opioid-induced hyperthermia because a prostaglandin synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to administration of peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine and beta-endorphin since naloxone attenuated the effect. In contrast, the hyperthermic responses to ketocyclazocine, SKF 10,047, pentazocine, Met-enkephalin, Leu-enkephalin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin were not antagonized by naloxone. Lack of antagonism of naloxone on pyrogen, arachidonic acid, PGE2, dibutyryl cAMP and NE-induced hyperthermia indicates that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004723:Endorphins / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007458:Iodipamide / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D004723:Endorphins; D009294:Narcotics; D010643:Phenoxybenzamine; D009270:Naloxone; D013806:Theophylline; D007458:Iodipamide; D009638:Norepinephrine; D007213:Indomethacin