Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present experiments were performed to investigate the effects of the selective mu opioid receptor antagonist, beta-funaltrexamine (beta-FNA), on the physical dependence liability of butorphanol (a mixed agonist/antagonist opioid analgesic). Butorphanol (26 nmol/microliter/h) was continuously infused via osmotic minipumps into the lateral cerebral ventricle of male Sprague-Dawley rats for 72 h. beta-FNA (12, 24, and 48 nmol/5 microliter/rat) was administered ICV 3 h prior to and 48 h after initiation of the butorphanol infusion. Treatment with beta-FNA significantly diminished naloxone-induced escape behavior, hypothermia, and loss of body weight in a dose-dependent manner, while naloxone-induced teeth-chattering, forepaw tremors, and urination were also reduced, but in a dose-independent manner. These results suggest that the mu opioid receptor is partially involved in the development of physical dependence upon butorphanol.
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PMID:Effects of beta-funaltrexamine on butorphanol dependence. 152 43

Previous studies showed that parenterally administered morphine at 4-16 mg/kg markedly increased body temperature in the rat, but higher doses of morphine (> or = 30 mg/kg, subcutaneously, sc) caused a profound decrease in body temperature. Based on the use of selective opioid agonists and antagonists, we postulated that these effects were due to morphine's actions on mu and kappa receptors, respectively. In the present study, we sought to determine whether an antisense (AS) oligodeoxynucleotide (oligo) against cloned mu or kappa opioid receptors could affect morphine-induced body temperature changes. AS oligos were directed against nucleotides 1-18 of the coding region of the mu receptor and 4-21 of the coding region of the kappa receptor. Male SD rats were surgically implanted with intracerebroventricular (icv) cannulae. Rats received icv injections of vehicle or oligo in the animal colony room on days 1, 3 and 5. Either AS oligo or missense (MS) oligo was infused in a volume of 5 microliters over 30 s to freely moving animals. On day 6, the rats were tested. The results showed that icv treatment with an AS oligo against mu opioid receptors, but not an MS oligo against the mu opioid receptor or an AS oligo against the kappa opioid receptor, significantly attenuated the hyperthermia normally produced by a relatively low dose of morphine administered sc. In addition, treatment with an AS oligo against kappa receptors, but not an MS oligo against kappa opioid receptor or an AS oligo against the mu opioid receptor, significantly blocked the hypothermia induced by a high dose of morphine. This study confirms our earlier postulate that morphine at 4 mg/kg, sc, induces an increase in body temperature primarily via mu opioid receptors in the brain and a high dose (30 mg/kg) of morphine administered sc produces a decrease primarily through kappa opioid receptors in the brain.
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PMID:Antisense confirmation of mu- and kappa-opioid receptor mediation of morphine's effects on body temperature in rats. 902 67

Previous studies demonstrated that intracerebroventricular (icv) injection of a kappa opioid receptor agonist decreased, and a mu agonist increased, body temperature (Tb) in rats. A dose-response study with the selective kappa antagonist nor-binaltorphimine (nor-BNI) showed that a low dose (1.25 nmol, icv) alone had no effect, although a high dose (25 nmol, icv) increased Tb. It was hypothesized that the hyperthermia induced by nor-BNI was the result of the antagonist blocking the kappa opioid receptor and releasing its inhibition of mu opioid receptor activity. To determine whether the Tb increase caused by nor-BNI was a mu receptor-mediated effect, we administered the selective mu antagonist CTAP (1.25 nmol, icv) 15 min after nor-BNI (25 nmol, icv) and measured rectal Tb in unrestrained rats. CTAP significantly antagonized the Tb increase induced by icv injection of nor-BNI. Injection of 5 or 10 nmol of CTAP alone significantly decreased the Tb, and 1.25 nmol of nor-BNI blocked that effect, indicating that the CTAP-induced hypothermia was kappa-mediated. The findings strongly suggest that mu antagonists, in blocking the basal hyperthermia mediated by mu receptors, can unmask the endogenous kappa receptor-mediated hypothermia, and that there is a tonic balance between mu and kappa opioid receptors that serves as a homeostatic mechanism for maintaining Tb.
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PMID:The dynamic relationship between mu and kappa opioid receptors in body temperature regulation. 1625 20

Mammals maintain a nearly constant core body temperature (Tb) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering Tb [1-6]. This adaptive response conserves energy, limiting the loss of body weight due to low calorie intake [7-10]. Here we show that this response is regulated by the kappa opioid receptor (KOR). CR is associated with increased hypothalamic levels of the endogenous opioid Leu-enkephalin, which is derived from the KOR agonist precursor dynorphin [11]. Pharmacological inhibition of KOR, but not of the delta or the mu opioid receptor subtypes, fully blocked CR-induced hypothermia and increased weight loss during CR independent of calorie intake. Similar results were seen with DIO mice subjected to CR. In contrast, inhibiting KOR did not change Tb in animals fed ad libitum (AL). Chemogenetic inhibition of KOR neurons in the hypothalamic preoptic area reduced the CR-induced hypothermia, whereas chemogenetic activation of prodynorphin-expressing neurons in the arcuate or the parabrachial nucleus lowered Tb. These data indicate that KOR signaling is a pivotal regulator of energy homeostasis and can affect body weight during dieting by modulating Tb and energy expenditure.
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PMID:Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss. 3184 84