The role of endogenous opioids as mediators of the hypothermic effects of intrathecally administered calcium and calcitonin gene-related peptide in mice.
To the authors' knowledge, the effect of i.t. administered calcium on thermoregulation in mice has not been investigated. Calcium administration (i.t.) induced hypothermia in mice. It was found that calcitonin gene-related peptide (CGRP) (i.t.) also produced hypothermia. Because opioids have well documented thermoregulatory effects, the authors evaluated whether the hypothermia induced by calcium and CGRP was the result of the release of opioids. Calcium induced hypothermia at different ambient temperatures (4 degrees C, 22 degrees C and 30 degrees C) in intact mice. Similarly treated spinalized mice maintained body temperature. Using laser Doppler flowmetry, there was a significant increase in blood flow in the tails of calcium-injected mice vs. those of vehicle-injected mice. Both naloxone and naltrindole failed to block the hypothermic effects of calcium (i.t.). Nor-binaltorphimine (i.t.) significantly blocked calcium (i.t.)-induced changes in body temperature. CGRP (i.t.) produced hypothermia for 15 hr postinjection, with the maximum decrease at 3 hr. CGRP induced hypothermia in intact and sham-lesioned mice but not in spinalized mice. CGRP (i.c.v.) also produced hypothermia (onset, 15-min postinjection) followed by the peak effect at 1 hr with recovery to baseline temperature by 2 hr. Subthreshold doses of calcium and CGRP given in combination produced greater than additive hypothermia. The hypothermic effects of CGRP were reversed by naloxone, naltrindole and nor-binaltorphimine. CGRP produced significant hypothermia in both morphine-tolerant and nontolerant mice. Chronic administration of CGRP in nontolerant and morphine-tolerant mice did not alter hypothermia after pretreatment with CGRP (i.t.).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond.
F L
FL
Smith
S P
SP
Welch
D S
DS
Dombrowski
W L
WL
Dewey
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004723:Endorphins / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007036:Hypothermia, Induced; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D004723:Endorphins; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C055382:naltrindole; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium