Effect of ambient temperature on the ability of mu-, kappa- and delta-selective opioid agonists to modulate thermoregulatory mechanisms in the rat.
Tyr-Pro-N-MePhe-D-Pro-NH2 (1.86 nmol), dynorphin A1-17 (4.65 nmol) and DPDPE (4.64 nmol), which are selective for mu-, kappa- and delta- opioid receptors, respectively, were injected into the right lateral ventricle of unrestrained male Sprague-Dawley rats. At ambient temperatures of 30 degrees C and 5 degrees C, brain surface temperature (Tb), oxygen consumption (VO2) and heat exchange (Q) were measured for 3 hr after injection in a gradient-layer calorimeter. Tyr-Pro-N-MePhe-D-Pro-NH2 at 30 degrees C caused significant hyperthermia (1.39 +/- 0.48 degree C) with onset occurring 15 to 30 min after injection and lasting 60 min after injection. Increased Tb was due to a significant decrease in Q (-1.31 +/- 0.31 cal/g/hr) and to a 60 to 75% increase in VO2 compared with saline controls. Thirty-min pretreatment with cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (0.74 nmol), a mu-selective antagonist, blocked the changes. At 30 degrees C, neither dynorphin A1-17 nor DPDPE significantly altered Tb, Q or VO2. At 5 degrees C ambient, Tyr-Pro-N-MePhe-D-Pro-NH2 decreased VO2, resulting in hypothermia (-1.01 degree +/- 0.46 degree C). Q was significantly reduced during the same period. Postinjection thermoregulatory responses to i.c.v. injection of dynorphin A1-17 at 5 degrees C varied widely from animal to animal, and lethality (33%, within 60 min after injection) became a significant factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Handler
C M
CM
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania.
Piliero
T C
TC
Geller
E B
EB
Adler
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004723:Endorphins / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009294:Narcotics / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D013696:Temperature
D004723:Endorphins; D004745:Enkephalins; D009294:Narcotics; D010455:Peptides; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C009862:connective tissue-activating peptide; C044708:morphiceptin, N-Me-Phe(3)-; D020881:Enkephalin, D-Penicillamine (2,5)-