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)

In the present work, the effects of neurotransmitter antagonists on theophylline-induced changes in body temperature were investigated. Intraperitoneal (i.p.) administration of a low dose of theophylline (25 mg/kg) induced slight hyperthermia, while high doses (75 and 100 mg/kg) induced hypothermia. The hypothermic effect of theophylline was decreased by pretreatment of animals with the dopamine D2 receptor antagonists sulpiride (15 and 30 mg/kg i.p.) and pimozide (0.125 and 0.25 mg/kg i.p.), the muscarinic receptor antagonist atropine (2.5 and 5 mg/kg i.p.) and the 5-HT receptor antagonist metergoline (0.25 mg/kg i.p.). However, the dopamine D1 receptor antagonist SCH 23390 (0.05 and 0.5 mg/kg i.p.), the alpha-adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg i.p.) did not after the theophylline response. In reserpinized mice, theophylline caused a dose-dependent rise in body temperature. The response was blocked in animals pretreated with phenoxybenzamine, propranolol and atropine. Single treatment of animals with either SCH 23390 or sulpiride, and also with a combination of the two drugs, decreased the hyperthermia induced by theophylline in reserpinized mice. Pimozide or metergoline did not have any effect in this respect. These data suggest that the hypothermic response to theophylline may be mediated through dopaminergic, cholinergic and serotonergic mechanisms. The hyperthermic action of theophylline in reserpinized animals may be mediated through dopaminergic, cholinergic and adrenergic systems. Overall it seems likely that theophylline interacts with modulatory mechanisms involved in thermoregulation.
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PMID:On the mechanisms by which theophylline changes core body temperature in mice. 808 93

Tachyphylaxis develops to the hypertensive response to central (i.c.v.) injection of carbachol in conscious rats. This pressor response exhibits tachyphylaxis if the injection is repeated within 8 hr of the first injection. Blockade of brain prostaglandin synthesis with indomethacin does not inhibit the pressor response to carbachol in naive rats, but eliminates the pressor response to carbachol when the muscarinic agonist is repeated within a few hours of the first injection. If the time interval is extended to permit return of the full response (i.e., 24 hr later), indomethacin no longer inhibits the pressor response. The related cyclooygenase inhibitor meclofenamate produced effects which were identical to those of indomethacin, but at approximately 10-fold higher doses. When shorter acting drugs (duration of action < 30 min), physostigmine or arecoline, were used according to the same paradigm, indomethacin was less effective at inhibiting the pressor response to the second injection, even when the two agonist injections were spaced only 30 min apart. The ability of indomethacin to enhance central muscarinic receptor tachyphylaxis was also observed in carbachol-induced hypothermia. The density of diencephalic muscarinic receptors was estimated by using N-[3H]methylscopolamine as a probe. Carbachol-induced a down-regulation of muscarinic receptors, and indomethacin increased the extent of this down regulation. These findings suggest that prostaglandins play a role in the development of tachyphylaxis to brain muscarinic receptor stimulation: activation of prostaglandin synthesis may decelerate the development of desensitization to muscarinic agonists.
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PMID:Role of prostanoids in the regulation of central cholinergic receptor sensitivity. 833 66

The object of the study was to determine the pharmacological nature of pinacolyl methylphosphonofluoridate (soman)-induced hypothermia in mice. This was accomplished by examining the soman hypothermia dose response and the effect of various pharmacological antagonists in comparison to the hypothermia responses of muscarinic and nicotinic cholinergic agonists such as oxotremorine and nicotine and another anticholinesterase, physostigmine. Core temperature in mice was monitored by telemetry. In general, atropine antagonized oxotremorine, physostigmine, and soman hypothermia but not nicotine hypothermia whereas mecamylamine antagonized nicotine hypothermia but not that produced by the other agonists. Soman hypothermia was not affected significantly by various pharmacological antagonists, suggesting that other neurotransmitters were not involved in the expression of soman hypothermia. Soman hypothermia appears to be due to muscarinic receptor stimulation and can be effectively antagonized, but not completely, by the use of atropine. Acetylcholinesterase oxime reactivators, such as HI-6 and toxogonin, were ineffective in antagonizing soman-induced hypothermia and reactivating hypothalamic acetylcholinesterase, whereas HI-6 was effective in reactivating soman-inhibited diaphragm acetylcholinesterase when administered up to 10 min after soman, indicating that aging of the soman-inhibited acetylcholinesterase had not occurred. Soman hypothermia appears to be primarily a muscarinic receptor-related event.
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PMID:Pharmacological nature of soman-induced hypothermia in mice. 845 Dec 71

Both oxotremorine and physostigmine both in doses ranging from 25 to 100 micrograms/kg produced dose-dependent attenuation of withdrawal jumping and potentiation of 'wet dog' shakes, burrowing, hypothermia and body weight loss precipitated by naloxone (1 mg/kg, i.p.) in morphine-dependent mice. On the other hand, atropine sulphate (2-20 mg/kg) dose-dependently attenuated all naloxone precipitated withdrawal symptoms except withdrawal hypothermia which was further potentiated. However, the peripherally acting derivative atropine methyl nitrate (2-10 mg/kg) also attenuated all naloxone-induced withdrawal symptoms except jumping, which was not significantly modified. Hyoscine (0.2-20 mg/kg) exhibited a biphasic effect on withdrawal jumping. Withdrawal jumping was potentiated by low and attenuated by high doses of hyoscine. Withdrawal body weight loss was dose-dependently attenuated but 'wet dog' shakes, burrowing and hypothermia were markedly potentiated by hyoscine. Our results suggest that a combination of central muscarinic activation and peripheral muscarinic blockade can partially ameliorate precipitated morphine withdrawal. Differences observed between atropine and hyoscine with regard to their modifying effects on withdrawal symptoms may be explained on the basis that the drugs may be acting on the different subpopulations of the muscarinic receptor or through non-cholinergic systems.
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PMID:The role of cholinergic systems in the expression of morphine withdrawal. 882 52

Oxotremorine is a muscarinic receptor agonist that induces a variety of physiological and behavioural effects including hypothermia in mice. These effects are antagonized dose-dependently by classical anticholinergic compounds such as atropine. Although the oxotremorine-induced hypothermic response has been demonstrated in mice, few studies of the effects of this muscarinic agonist have been made in the rat. The following studies were made in male Sprague Dawley rats: 1. an investigation of the dose-response relationship between oxotremorine and hypothermia; 2. an examination of the effect of housing on the oxotremorine-induced hypothermic response, and 3, an investigation of the acute administration of various doses of atropine sulphate on the hypothermia caused by oxotremorine. The results indicate that the dose-response relationship between oxotremorine and the antagonism of hypothermia is similar in rat as it is in mice. The results also showed that this effect did not occur in group-housed animals.
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PMID:The characterization of oxotremorine-induced hypothermic response in the rat. 893 56

Central administration of galanin dose-dependently (minimum effective dose, M.E.D. = 1 nmol) blocked the hypothermia induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg s.c.), in mice. This inhibitory effect was reversed by pretreatment with the galanin receptor antagonist galantide (0.3 nmol) and also by pretreatment with the ATP-sensitive potassium channel blockers glibenclamide (10 nmol) and gliquidone (10 nmol). The hypothermic response to 8-OH-DPAT was also blocked by the 5-HT1A receptor antagonist (N-(2,4(2-methoxyphenyl)-1-piperazinyl)ethyl-N-(2-pyridinyl)cyclohexane, (WAY 100,635, M.E.D. = 0.01 mg/kg s.c.), and the centrally acting muscarinic receptor antagonist scopolamine (M.E.D. = 10 mg/kg i.p.) but not the peripheral muscarinic receptor antagonist N-methylscopolamine. 8-OH-DPAT (0.5 mg/kg s.c.) also decreased cortical and hypothalamic 5-HT (5-hydroxytryptamine, serotonin) metabolism, an effect which was not blocked by pretreatment with galanin (0.3-3 nmol intracerebroventricular, i.c.v.). Neither did galanin (0.03-3 nmol/5 microliters i.c.v.) affect basal 5-HT metabolism in these brain regions. Furthermore, pretreatment in vitro of mouse cortical membranes with galanin (10 or 1000 nM) had no effect on 5-HT1A receptor affinity, Bmax or pharmacology determined using [3H]8-OH-DPAT. These results suggest that the inhibition of 8-OH-DPAT induced hypothermia by galanin is probably not mediated by an interaction with 5-HT1A receptors but more likely by blocking the indirect activation by 8-OH-DPAT of central cholinergic pathways involved in temperature regulation.
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PMID:Effects of galanin on 8-OH-DPAT induced decrease in body temperature and brain 5-hydroxytryptamine metabolism in the mouse. 899 1

Choline (75-300 microg) produced dose-dependent hypothermia when injected intracerebroventricularly (i.c.v.). Pre-treatment with the muscarinic receptor antagonist, atropine (10 microg, i.c.v.), blocked the hypothermic effect of choline (150 microg), but the response was only partially attenuated by pre-treatment with the nicotinic receptor antagonist, mecamylamine (20 microg, i.c.v.). Pirenzepine (25 microg), a muscarinic M1 receptor antagonist, or hexahydro-siladifenidol (HHSD) (100 microg), a muscarinic M3 receptor antagonist, also blocked choline-induced hypothermia when injected centrally. Unlike the other muscarinic receptor antagonists, M2-selective 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyri do[2,3-b][1,4]benzodiazepin-6-one (AF-DX116) (10 microg), did not affect choline-induced hypothermia. We also found that choline-induced hypothermia was very sensitive to the ambient temperature. Similar to its effect at room temperature, choline produced dose-dependent hypothermia at 4 degrees C, but this effect was abolished at 32 degrees C. These data suggest that choline produces hypothermia and this effect is mediated by muscarinic receptors.
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PMID:The effects of choline on body temperature in conscious rats. 988 77

Muscarinic acetylcholine receptors (M(1)-M(5)) regulate many key functions of the central and peripheral nervous system. Primarily because of the lack of receptor subtype-selective ligands, the precise physiological roles of the individual muscarinic receptor subtypes remain to be elucidated. Interestingly, the M(4) receptor subtype is expressed abundantly in the striatum and various other forebrain regions. To study its potential role in the regulation of locomotor activity and other central functions, we used gene-targeting technology to create mice that lack functional M(4) receptors. Pharmacologic analysis of M(4) receptor-deficient mice indicated that M(4) receptors are not required for muscarinic receptor-mediated analgesia, tremor, hypothermia, and salivation. Strikingly, M(4) receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses (as compared with their wild-type littermates) after activation of D1 dopamine receptors. These results indicate that M(4) receptors exert inhibitory control on D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are coexpressed at high levels. Our findings offer new perspectives for the treatment of Parkinson's disease and other movement disorders that are characterized by an imbalance between muscarinic cholinergic and dopaminergic neurotransmission.
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PMID:Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice. 1053

G protein-coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein-coupled receptors (GPCR). To address the physiological importance of GRK5-mediated regulation of GPCRs, mice bearing targeted deletion of the GRK5 gene (GRK5-KO) were generated. GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon challenge with the nonselective muscarinic agonist oxotremorine. Classical cholinergic responses such as hypothermia, hypoactivity, tremor, and salivation were enhanced in GRK5-KO animals. The antinociceptive effect of oxotremorine was also potentiated and prolonged. Muscarinic receptors in brains from GRK5-KO mice resisted oxotremorine-induced desensitization, as assessed by oxotremorine-stimulated [5S]GTPgammaS binding. These data demonstrate that elimination of GRK5 results in cholinergic supersensitivity and impaired muscarinic receptor desensitization and suggest that a deficit of GPCR desensitization may be an underlying cause of behavioral supersensitivity.
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PMID:Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice. 1062 64

Muscarinic acetylcholine receptors (M1-M5) play important roles in the modulation of many key functions of the central and peripheral nervous system. To explore the physiological roles of the two Gi-coupled muscarinic receptors, we disrupted the M2 and M4 receptor genes in mice by using a gene targeting strategy. Pharmacological and behavioral analysis of the resulting mutant mice showed that the M2 receptor subtype is critically involved in mediating three of the most striking central muscarinic effects, tremor, hypothermia, and analgesia. These studies also indicated that M4 receptors are not critically involved in these central muscarinic responses. However, M4 receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses following drug-induced activation of D1 dopamine receptors. This observation is consistent with the concept that M4 receptors exert inhibitory control over D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are known to be coexpressed. These findings emphasize the usefulness of gene targeting approaches to shed light on the physiological and pathophysiological roles of the individual muscarinic receptor subtypes.
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PMID:Generation and pharmacological analysis of M2 and M4 muscarinic receptor knockout mice. 1139 13


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