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 intracerebroventricular (i.c.v.) administration of pertussis toxin (0.5 microgram) to rats significantly reduced the hypothermic and behavioural effects (episodic bizarre postures characterized by limb rigidity and followed by barrel rolling) induced by i.c.v. dynorphin A (10 micrograms). These central effects of dynorphin A thus appear to be initiated at a receptor site that interacts with G proteins substrates sensitive to pertussis toxin. Dynorphin A-induced hypothermia was also significantly reduced by i.c.v. pretreatment with the Ca2+ antagonist, verapamil (10 micrograms), although verapamil per se did not modify the behavioural effects elicited by the peptide.
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PMID:Gi proteins and calcium in dynorphin-induced hypothermia and behaviour. 197 19

Prodynorphin-derived peptides were tested for their effects on body temperature after intracerebroventricular administration to unrestrained male rats. Dynorphin A (Dyn A) (5 and 10 nmol) and Dynorphin A-(1-32) (Dyn A-(1-32) (2.5 and 5 nmol) lowered body temperature with a maximum approximately 30 min after administration. Dyn B (up to 50 nmol) did not induce hypothermia. Lower doses of all peptides did not alter body temperature. The hypothermic effect was significantly, but not completely prevented by MR1452 (30 nmol), a preferential antagonist of the kappa receptor, administered intracerebroventricularly. Naloxone, a mu receptor antagonist, naltrexone, its long acting analog up to doses of 100 nmol, as well as MR1453, the (+)-enantiomer of kappa antagonist MR1452 with no opioid binding properties, did not prevent the hypothermic effect. Moreover, episodic barrel rolling and bizarre postures elicited by Dyn A and Dyn A-(1-32) were reduced in rats pretreated i.c.v. with MR1452 (30 nmol), but not with naloxone (up to 100 nmol). Interestingly, des-Tyr-Dynorphin A (Dyn A-(2-17)), a fragment with virtually no opioid binding potential, was 4 times less potent that Dyn A in inducing hypothermia. These findings are consistent with the hypothesis that prodynorphin-derived peptides effects are not exclusively opioids in nature.
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PMID:Hypothermia elicited by some prodynorphin-derived peptides: opioid and non-opioid actions. 257 Nov 7

Gammahydroxybutyrate is a naturally occurring metabolite of many mammalian tissues. Although its administration produces a wide range of pharmacological effects, its normal function has never been clearly defined. GHB can induce NREM and REM sleep, anaesthesia, hypothermia, and a trance-like state which has been considered a model for petit mal epilepsy. It markedly increases brain dopamine levels. It has been touted as a central neurotransmitter or neuromodulator, and high affinity brain receptors, as well as central mechanisms for its synthesis, uptake and release have been demonstrated in support of this. But GHB is also found in many peripheral tissues and in some of these in higher concentrations than in the brain. No explanation has been offered for its presence in these tissues. A number of studies indicate that GHB can reduce energy substrate consumption in both brain and peripheral tissues, and that it can protect these tissues from the damaging effects of anoxia or excessive metabolic demand. Indeed there is some evidence to suggest that endogenous GHB levels rise under these circumstances. GHB appears to act through the endogenous opioid system, since in the brain, at least, GHB raises dynorphin levels and its metabolic and pharmacological effects can be blocked by naloxone. These, and other observations detailed in this review, suggest that GHB may function naturally in the induction and maintenance of physiological states, like sleep and hibernation, in which energy utilization is depressed. GHB may also function naturally as an endogenous protective agent when tissue energy supplies are limited.
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PMID:Gammahydroxybutyrate: an endogenous regulator of energy metabolism. 269 26

Intracerebroventricular administration of 20, 40 and 60 nmol of dynorphin (1-13) produced analgesia, as assessed by flinch/jump response to footshock, and hypothermia in the rat. Rats developed tolerance to both the analgesic and thermic effects of the 20 nmol dose of dynorphin. Dynorphin and beta-endorphin showed cross-tolerance with respect to their analgesic but not their thermic effects. Dynorphin and morphine also produced cross-tolerant analgesic effects. Naloxone (10 mg/kg, IP) completely blocked the barrel rolling produced by 20 nmol dynorphin but did not alter its analgesic or thermic effects.
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PMID:Dynorphin (1-13): analgesia, hypothermia, cross-tolerance with morphine and beta-endorphin. 628 45

Neurotensin (NT) administered intracerebroventricularly (i.c.v.) to rats, blocks intestinal transit (tested by charcoal meal) in linear relation to the log of the doses within the range of 0.6-2.5 nmoles/rat. NT in this test is about 40 times more active than morphine (M) and 6 times less active than dermorphin (DM) on a molar basis. Within this dose range NT does not induce analgesia (tail-flick test) or hypothermia (tested at 22 degrees C). The intestinal effect can also be elicited by injecting the peptide into the periaqueductal gray matter (PAG). NT injected intraperitoneally (i.p.) is inactive up to doses 4 times the maximal active i.c.v. dose. Naloxone (Nx) and dynorphin 1-13 could not antagonize the intestinal effect of i.c.v. NT. The relationship between this central intestinal effect and many other central effects of NT is discussed.
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PMID:Effect on intestinal transit of neurotensin administered intracerebroventricularly to rats. 666 30

To examine the role of neurotensin in opioid-induced thermo-regulation, Tyr-Pro-N-MePhe-D-Pro-NH2 (PL-017, 1.86 nmol i.c.v.), neurotensin (NT, 0.0747-2.98 nmol i.c.v.), ([trans-(+/-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzenacetamide+ ++]) (U50,488H; U50, 10-40 mg/kg s.c.), dynorphin A1-17 (DY, 4.65 nmol i.c.v.) and DPDPE (4.65 nmol i.c.v.) were injected alone or in combination with NT into unrestrained, male S-D rats. At 20 +/- 2 degrees C ambient, body temperature (Tb) was measured for 3 hr after injection. PL-017 induced dose-dependent hyperthermia; NT, DY and U50 produced dose-related hypothermia. NT (0.0747 nmol) had no effect on PL-017-induced hyperthermia; higher doses of PL-017/NT antagonized the hyperthermia and increased the peak and duration of the hypothermia. Pretreatment with cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 0.74 nmol i.c.v.) blocked the enhanced PL-017/NT-induced hypothermia but had no effect on NT-induced hypothermia. DY/NT reduced Tb dose dependently but the effect did not differ significantly from NT alone. U50 (20 or 40 mg/kg)/NT increased the peak and duration of the hypothermic response. Naloxone pretreatment (10 mg/kg s.c.) blocked the effect of U50 alone and in combination with NT, as did the peripheral opioid antagonist, naloxone methiodide (100 mg/kg s.c.). Nor-binaltorphimine (25 nmol i.c.v.) partially blocked the effect of U50 on Tb and had no effect on NT or U50/NT. DPDPE did not alter Tb alone or in combination with NT. The data presented provide information on the role of NT in opioid-induced thermoregulation.
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PMID:Interaction between opioid agonists and neurotensin on thermoregulation in the rat. I. Body temperature. 761 10

This study with the rat evaluated the contribution of omega-conotoxin GVIA-(omega-CgTx) and verapamil-sensitive Ca2+ channels in behavioural, antinociceptive and thermoregulatory responses to intracerebroventricular (i.c.v.) injection of [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) and dynorphin A-(1-17), which are selective agonists for putative mu, delta and kappa-opioid receptors, respectively. The rats treated with omega-CgTx (8-32 pmol i.c.v.) showed transient, dose-dependent shaking behaviour, hyperalgesia and hypothermia which gradually disappeared within 4 h. The behaviour of the rats was normal by 24 h. Histological examination of brain sections showed morphological alterations of neurons in the hippocampus, medial-basal hypothalamus and pyriform cortex. antinociception, catalepsy and thermoregulatory responses elicited by DAMGO (0.4 and 2.0 nmol) were significantly prolonged and potentiated by verapamil (20 pmol i.c.v. 15 min before) or omega-CgTx (8 pmol 24 h before). Antinociception and hypothermia induced by DPDPE were antagonized by verapamil and omega-CgTx, whereas only omega-CgTx prevented the behavioural arousal observed after DPDPE. Similarly, hypothermia induced by dynorphin A-(1-17) (5.0 nmol) and by the kappa-opioid receptor agonist U50,488H (215 nmol) was antagonized by the two Ca2+ channel blockers but only omega-CgTx prevented the barrel rolling and bizarre postures caused by the opioid peptide.
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PMID:Effect of omega-conotoxin and verapamil on antinociceptive, behavioural and thermoregulatory responses to opioids in the rat. 801 57

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)
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PMID:Effect of ambient temperature on the ability of mu-, kappa- and delta-selective opioid agonists to modulate thermoregulatory mechanisms in the rat. 811 97

The rate of lipid peroxidation was studied in rat brain, liver, skeletal muscles and myocardial tissues in dynamics of hypothermia. Cooling of the animals down to 30 degrees induced lipid peroxidation, which was markedly expressed within 3-hour continuation of the treatment. Profound hypothermia (20 degrees) increased levels of malonic dialdehyde in the tissues studied by 30-160%, while prolongation of the impairment up to 3 hrs resulted in normalization of the lipid peroxidation parameters studied. The artificial hexapeptide dalargin, similar to leu-enkephalin, inhibited the rate of lipid peroxidation in profound hypothermia both in vivo and in vitro.
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PMID:[The effect of hypothermia and dalargin on lipid peroxidation in rat tissues]. 833 82

PL017 and dynorphin A1-17 were shown previously to cause a marked increase and a profound decrease in body temperature (Tb), respectively. In this study, we examined whether an antisense (AS) oligodeoxynucleotide (oligo) against cloned mu or kappa opioid receptors could block PL017- or dynorphin A-induced body temperature changes. Treatment with an AS oligo against mu receptors, but not sense (S) oligo, missense (MS) oligo or artificial cerebrospinal fluid (aCSF), abolished PL017-induced hyperthermia. In addition, treatment with an AS oligo against kappa receptors, but not S oligo, MS oligo or aCSF, greatly attenuated dynorphin A-induced hypothermia. This study further supports the notion that mu and kappa receptors mediate Tb regulation.
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PMID:Antisense oligodeoxynucleotides against mu- or kappa-opioid receptors block agonist-induced body temperature changes in rats. 854 17


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