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)

Phase I Coxiella burnetii antigen isolated by phenol extraction from purified suspensions of C. burnetii in phase I is a complex lipopolysaccharide (LPS) molecule containing substances typical of the bacterial LPS. Some endotoxic properties of this C. burnetii LPS, namely pyrogenicity and skin epinephrine reaction in rabbits, hypothermia in white rats, lethal effect on chicken embryos or on actinomycin-D-treated mice are similar to those of LPS isolated from other Gram-negative bacteria.
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PMID:Characterization of an endotoxic lipopolysaccharide from Coxiella burnetii. 0 71

A lipophilic thermostable lipopolysaccharide (LPS) complex was isolated by phenol extraction from purified suspensions of the typhus group rickettsiae. The LPS complex is antigenic and possesses some endotoxic properties such as toxicity for actinomycin D-treated mice, pyrogenicity for rabbits and guinea pigs, ability to elicit hypothermia in white rats and local Schwartzman reaction and active cutaneous anaphylaxis in rabbits.
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PMID:Some biological properties of an endotoxic lipopolysaccharide from the typhus group rickettsiae. 2 40

The effects of drug treatment and of cold-restraint stress (a method used to produce experimental stomach ulcers) on gastric emptying of a resin (colestipol-phenol red complex) were investigated in rats. Gastric emptying was decreased by intraperitoneal treatment with atropine (0.3 mg/kg) or verapamil (4 mg/kg), and enhanced by bethanechol (1.2 mg/kg). Stress by restraint at 4 degrees C for 2 hr markedly reduced gastric emptying; the pattern of effects of drug pretreatment in these stressed rats was similar to that seen in their nonstressed controls. Further experiments, with stress for 3 hr, revealed that the gastric emptying rate was triphasic; increasing in the first hr, returning to normal and then slowing in the third hr of stress. Initial increase in emptying rate was probably due to predominant vagal overactivity. Hypothermia and possibly other factors induced by cold-restraint stress could have subsequently depressed gastric motility.
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PMID:The effect of cold-restraint stress on gastric emptying in rats. 286 65

Morphine administration (20 mg/kg s.c.) slowed renal elimination of phenol red in mice, raising plasma levels of this dye and reducing its levels in urine. After 9 days of twice daily morphine injections up to 100 mg/kg, an acute 20 mg/kg morphine challenge did not produce analgesia or hypothermia as in naive mice. This multiple dose morphine regimen also induced tolerance to the effects of the narcotic on plasma and urine levels of phenol red. Morphine, 20 mg/kg, reduced plasma p-aminohippurate clearance by 72% in naive mice but only by 56% in tolerant mice. However, reduction of iothalamate clearance after an acute morphine challenge did not show a statistically significant difference between naive and tolerant mice. These findings suggest that tolerance is more readily induced to the effects of narcotic on renal blood flow and/or tubular function than to reduction of glomerular filtration. Tolerance to the acute effects of morphine on phenol red disposition is probably due to lessened response of blood flow or tubular function in chronically dosed mice.
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PMID:Tolerance to morphine effects on renal disposition of xenobiotics in mice. 377 98

Transport of the anionic herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) was examined in vitro via the isolated choroid plexus of adult and neonatal rabbits and in vivo via ventriculocisternal perfusion. In vitro, the facilitated transport of 2,4-D by the choroid plexus was established in the rabbit by as early as 3 days of age. Uptake in both adults and neonates took place against a concentration gradient via a saturable process that was inhibited by ouabain and hypothermia (0 degrees C). Probenecid and hippuric acid were effective dose-dependent inhibitors of 2,4-D transport in vitro. The major metabolite of salicylate, salicyluric acid, was also an effective inhibitor, more than its precursor, salicylate, or gentisic acid, a second salicylate metabolite. Neither phenol, acetaminophen nor glycine inhibited 2,4-D transport. Thus, the effects appear specific for those compounds which share the organic acid transport system. The role of carrier-mediated transport in the clearance of 2,4-D from cerebrospinal fluid (CSF) was also evaluated in vivo by ventriculocisternal perfusion. Steady-state clearance of 2,4-D from CSF exceeded that of inulin and was reduced in a dose-dependent fashion in the presence of salicylate. Neither CSF formation nor absorption rates were changed. These results indicate that 2,4-D is transported from the CSF via the organic anion transport system, and that inhibitors of this transport system may block its elimination from the brain in vivo, just as they block its transport by the isolated choroid plexus.
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PMID:Saturable accumulation of the anionic herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), by rabbit choroid plexus: early developmental origin and interaction with salicylates. 686 28

The tetrahydrobenzindole, 2a-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl)-2a,3,4,5-tetrahydrobenzo[cd]indol-2(1H)-one (DR4004) has been described as a highly selective antagonist for the 5-hydroxytryptamine(7) (5-HT(7)) receptor [J. Med. Chem. 42 (1999) 533]. Consistent with original data, DR4004 bound to rat hypothalamic membranes with an affinity of 7.3+/-0.2 (pK(i)+/-S.E.M.) for the 5-HT(7) receptor. However, competition binding studies showed that DR4004 had poor receptor selectivity with the following affinity profile; dopamine D2 receptor, alpha(1)-adrenoceptor > or =5-HT(7) receptor>histamine H(1) receptor, alpha(2)-adrenoceptor>dopamine D1 receptor>beta-adrenoceptor, muscarinic and 5-HT(2A/C) receptors. In conscious rats DR4004 (1, 5 or 10 mg/kg i.p.) produced a dose-dependent hyperglycaemia and hypothermia, but the former was reduced by the dopamine D2 receptor antagonist raclopride. Another 5-HT(7) receptor antagonist, (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970) produced hypothermia but no hyperglycaemia. This study confirms that DR4004 has high affinity for the 5-HT(7) receptor but suggests that dopamine D2 receptor activity contributes to some of the in vivo effects.
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PMID:DR4004, a putative 5-HT(7) receptor antagonist, also has functional activity at the dopamine D2 receptor. 1216 13

We have shown previously that the severity of handling-induced convulsions during ethanol withdrawal was reduced in A2A receptor knock-out (A2AR-/-) mice. In the present report, we further characterize the role of adenosine A(2A) receptors in ethanol consumption and neurobiological responses to this drug of abuse. Male A2AR-/- mice showed increased consumption of solutions containing 6 and 20% (v/v) ethanol compared with wild-type (A2AR+/+) control mice; female A2AR-/- mice showed increased consumption of solutions containing 6 and 10% ethanol. This slightly higher ethanol consumption was also related to increased ethanol preference. In contrast, A2AR-/- mice showed normal consumption of solutions containing either sucrose or quinine. Relative to A2AR+/+ mice, A2AR-/- mice were found to be less sensitive to the sedative effect of 3.0 gm/kg ethanol, as measured by more rapid recovery from ethanol-induced loss of righting reflex, and to the hypothermic effects of 1.5, 3.0, and 4.0 gm/kg ethanol, although plasma ethanol levels did not differ significantly between the two genotypes. The selective adenosine A2A receptor antagonist ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (10-30 mg/kg) significantly attenuated ethanol-induced (4.0 gm/kg) hypothermia in CD1 mice. To assess whether ethanol administration would induce differential tolerance in A2AR-/- and wild-type mice, we administered ethanol (3.0 gm/kg) over 4 consecutive days and found no difference in the development of tolerance; however, female A2AR-/- mice showed a lower tolerance-acquisition rate. These data suggest that activating the A2A receptors may play a role in suppressing alcohol-drinking behavior and is associated with the sensitivity to the intoxicating effects of acute ethanol administration.
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PMID:Low ethanol sensitivity and increased ethanol consumption in mice lacking adenosine A2A receptors. 1245 Nov 48

gamma-Hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is proposed to function as a neurotransmitter or neuromodulator. gamma-Hydroxybutyrate and its prodrug, gamma-butyrolactone (GBL), recently received increased public attention as they emerged as popular drugs of abuse. The actions of GHB/GBL are believed to be mediated by GABAB and/or specific GHB receptors, the latter corresponding to high-affinity [3H]GHB-binding sites coupled to G-proteins. To investigate the contribution of GABAB receptors to GHB actions we studied the effects of GHB in GABAB(1)-/- mice, which lack functional GABAB receptors. Autoradiography reveals a similar spatial distribution of [3H]GHB-binding sites in brains of GABAB(1)-/- and wild-type mice. The maximal number of binding sites and the KD values for the putative GHB antagonist [3H]6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene acetic acid (NCS-382) appear unchanged in GABAB(1)-/- compared with wild-type mice, demonstrating that GHB- are distinct from GABAB-binding sites. In the presence of the GABAB receptor positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol GHB induced functional GTPgamma[35S] responses in brain membrane preparations from wild-type but not GABAB(1)-/- mice. The GTPgamma[35S] responses in wild-type mice were blocked by the GABAB antagonist [3-[[1-(S)-(3,4dichlorophenyl)ethyl]amino]-2-(S)-hydroxy-propyl]-cyclohexylmethyl phosphinic acid hydrochloride (CGP54626) but not by NCS-382. Altogether, these findings suggest that the GHB-induced GTPgamma[35S] responses are mediated by GABAB receptors. Following GHB or GBL application, GABAB(1)-/- mice showed neither the hypolocomotion, hypothermia, increase in striatal dopamine synthesis nor electroencephalogram delta-wave induction seen in wild-type mice. It, therefore, appears that all studied GHB effects are GABAB receptor dependent. The molecular nature and the signalling properties of the specific [3H]GHB-binding sites remain elusive.
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PMID:Specific gamma-hydroxybutyrate-binding sites but loss of pharmacological effects of gamma-hydroxybutyrate in GABA(B)(1)-deficient mice. 1465 21

Studies using selective drugs and knockout mice have demonstrated that the 5-HT(7) receptor plays an instrumental role in serotonin-induced hypothermia. There is also evidence supporting an involvement of the 5-HT(1A) receptor, although mainly from studies using 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT(1A/7) receptor agonist. Here we studied the effects of 8-OH-DPAT and selective antagonists for the 5-HT(1A) and 5-HT(7) receptors on body temperature in rats, wild-type (5-HT(7)(+/+)) mice and knockout (5-HT(7)(-/-)) mice. At lower doses (0.3-0.6 mg/kg, i.p.), 8-OH-DPAT decreased body temperature in 5-HT(7)(+/+) mice but not in 5-HT(7)(-/-) mice. At a higher dose (1 mg/kg, i.p.) 8-OH-DPAT induced hypothermia in both 5-HT(7)(-/-) and 5-HT(7)(+/+) mice. The 5-HT(1A) receptor antagonist (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2-phenylpropanamide (WAY-100135) (10 mg/kg, i.p.) inhibited the effect of 8-OH-DPAT at all doses in rats and mice. In 5-HT(7)(+/+) mice the selective 5-HT(7) receptor antagonist (R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970) (10 mg/kg, i.p.) fully inhibited the hypothermia induced by 0.3 mg/kg 8-OH-DPAT, but not that of higher doses. In rats, SB-269970 caused a 60% inhibition of the hypothermia induced by 0.3 mg/kg 8-OH-DPAT. Thus, both 5-HT(7) and 5-HT(1A) receptors are involved in a complex manner in thermoregulation, with the 5-HT(7) receptor being more important at lower, possibly more physiological, concentrations.
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PMID:8-OH-DPAT acts on both 5-HT1A and 5-HT7 receptors to induce hypothermia in rodents. 1503 84

LPS preparations cause a variety of body temperature (T(b)) responses: monophasic fever, different phases of polyphasic fever, and hypothermia. Conventional (c) LPS preparations contain highly active lipoprotein contaminants (endotoxin proteins). Whereas LPS signals predominantly via the Toll-like receptor (TLR) 4, endotoxin proteins signal via TLR2. Several TLR2-dependent responses of immunocytes to cLPS in vitro are triggered by endotoxin proteins and not by LPS itself. We tested whether any T(b) response to cLPS from Escherichia coli 055:B5 is triggered by non-TLR4-signaling contaminants. A decontaminated (d) LPS preparation (free of endotoxin proteins) was produced by subjecting cLPS to phenol-water reextraction. The presence of non-TLR4-signaling contaminants in cLPS (and their absence in dLPS) was confirmed by showing that cLPS (but not dLPS) induced IL-1beta expression in the spleen and increased serum levels of TNF-alpha and IL-1beta of C3H/HeJ mice; these mice bear a nonfunctional TLR4. Yet, both cLPS and dLPS caused cytokine responses in C3H/HeOuJ mice; these mice bear a fully functional TLR4. We then studied the T(b) responses to cLPS and dLPS in Wistar rats preimplanted with jugular catheters. At a neutral ambient temperature (30 degrees C), a low (0.1 microg/kg iv) dose of cLPS caused a monophasic fever, whereas a moderate (10 microg/kg iv) dose produced a polyphasic fever. In the cold (20 degrees C), a high (500 microg/kg iv) dose of cLPS caused hypothermia. All T(b) responses to dLPS were identical to those of cLPS. We conclude that all known T(b) responses to LPS preparations are triggered by LPS per se and not by non-TLR4-signaling contaminants of such preparations.
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PMID:Thermoregulatory responses of rats to conventional preparations of lipopolysaccharide are caused by lipopolysaccharide per se-- not by lipoprotein contaminants. 1586 Jun 47


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