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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the effects on sleep and brain temperature of bilateral microinjections of adenosine and adenosine analogs to the preoptic area (PO) of rats. Administration of adenosine (12.5 nmoles), a nonselective adenosine A1/A2 receptor agonist NECA (N-ethyl-carboxamido-adenosine, 1.0 nmole), and the selective adenosine A1 receptor agonist CPA (cyclopentyladenosine, 0.25, 0.5 nmoles) increased total sleep primarily through an enhancement in deep slow-wave sleep (SWS2), while adenosine also increased REM sleep. Administration of 12.5 nmoles adenosine and 0.25 nmoles CPA did not affect brain temperature, while 1.0 nmole NECA and 0.5 nmoles CPA caused a transient and prolonged hypothermia, respectively. Administration of the selective adenosine A2 receptor agonist CV-1808 (2-phenylaminoadenosine, 5, 10 nmoles) had no effect on sleep or brain temperature. The present results demonstrate a site for the central hypnotic action of adenosine, and a functional role for adenosine A1 receptors in the hypothalamus.
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PMID:Role of adenosine in sleep and temperature regulation in the preoptic area of rats. 178 Mar 43

Caffeine induces a dose-dependent decrease in core body temperature in mice and the hypothermia induced by a 100 mg/kg dose of caffeine was seen to persist for greater than 160 min. Other alkylxanthines including theophylline, enprophylline, isbutylmethylxanthine and 1,3-dipropyl-7-methylxanthine also showed dose-dependent reductions in body temperature. The dose of these drugs required to reduce body temperature by 2 degrees C was calculated and correlated with the affinities for the compounds at adenosine A1 and A2 receptors and their activities in inhibiting calcium dependent and independent phosphodiesterases. Significant relationships were found between the 2 degrees C hypothermic dose (HD2) and soluble and membrane calcium-independent phosphodiesterase inhibiting activity (r2s = 0.950 and 0.940, respectively). No significant relationship was seen between HD2 and soluble calcium-dependent phosphodiesterase inhibiting activity or with A2 adenosine receptor affinity. The relationship between HD2 and A1 adenosine receptor affinity (r2 = 0.739) did however almost reach statistical significance. These results would suggest that phosphodiesterase inhibition, instead of or in addition to adenosine receptor blockade, may play an important role in the effects of alkylxanthines on body temperature.
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PMID:Hypothermic effects of alkylxanthines: evidence for a calcium-independent phosphodiesterase action. 180 62

1. The effects of a range of adenosine receptor-selective ligands on body temperature were investigated following intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injection in conscious mice. The compounds tested were the non-selective adenosine receptor agonist 5'-N-ethyl-carboxamidoadenosine (NECA), the adenosine A1 receptor-selective agonists cyclopentyl-adenosine (CPA), N6-(9R-phenyl-isopropyl)-adenosine (R-PIA) and N-(1S,trans)-[2-hydroxyclopentyl]-adenosine (GR79236), the A2a receptor selective agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxyamidoaden osine (CGS-21680), the A2b receptor agonist N-[(2-methylphenyl)methyl[adenosine (metrifudil) and the A3 receptor agonist N6-(4-aminophenylethyl)adenosine (APNEA). 2. NECA (0.01-1 microgram, i.c.v.), all of the A1-selective agonists (0.01-1 microgram, i.c.v.) and APNEA (0.1-3 micrograms i.c.v.) produced profound and dose-related hypothermia and sedation. However, CGS-21680 (0.1-10 micrograms i.c.v.) and metrifudil (0.01-1 microgram i.c.v.), produced only mild hypothermia at the highest doses tested. 3. The hypothermic response to the A1 receptor-selective agonists, GR79236 and R-PIA was dose-dependently antagonized by peripheral administration of either the non-selective adenosine receptor antagonist, 8-phenyltheophylline (8-PT, approximately 40 and 30 fold rightward shifts of the dose-response curves respectively at 10 mg kg-1, i.p.), or the adenosine A1 receptor-selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, approximately 20 fold shift of the GR79236 dose-response curve at 1 mg kg-1, i.p.). The hypothermic response to APNEA was similarly dose-dependently antagonized by the A1 receptor-selective antagonist, DPCPX (5 fold shift at 0.1 mg kg-1, i.p.). 4.8(p-Sulphophenyl)theophylline (8-SPT, 10 and 30 mg kg-1, i.p.), a non-selective adenosine receptorantagonist that penetrates the blood brain barrier poorly, produced only modest antagonism (approximately 2 fold shift at 30 mg kg-1, i.p.) of the hypothermic response to GR79236.5. These data suggest that hypothermia induced by adenosine analogues in the conscious mouse is mediated via adenosine A1 receptors, which are probably located in the CNS.
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PMID:Characterization of the adenosine receptors mediating hypothermia in the conscious mouse. 788 96

1. Thermal responses to i.v. administration of N6-cyclohexyladenosine (CHA; 0.15 mg/kg), A1 adenosine receptor agonist, or 5'-N-ethylcarboxamidoadenosine (NECA; 0.15 mg/kg), A2 adenosine receptor agonist, were investigated in normothermic rabbits at an ambient temperature (Ta) of 20.0 +/- 1.0 degrees C. 2. Although both compounds inhibited metabolic heat production, only NECA produced hypothermia. 3. NECA showed strong hypotensive activity. 4. Both compounds produced vasoconstriction of the ear skin vessels and CHA, in addition, slowed down the respiratory rate. 5. The role of A1 or A2 adenosine receptors in the thermoregulatory activity of these compounds is discussed.
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PMID:The effect of N6-cyclohexyladenosine and 5'-N-ethylcarboxamidoadenosine on body temperature in normothermic rabbits. 872 28

To study the role of adenosine in sleep regulation, the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the antagonist caffeine were administered to rats. Intraperitoneal (i.p.) CPA 1 mg/kg but not 0.1 mg/kg, suppressed rapid-eye-movement (REM) sleep and enhanced electroencephalographic (EEG) slow-wave activity (power density 0.75-4.0 Hz) in non-REM sleep. The latter effect was remarkably similar to the response to 6-h sleep deprivation. The effects persisted when CPA-induced hypothermia was prevented. Caffeine (10 and 15 mg/kg i.p.) elicited a dose-dependent increase in waking followed by a prolonged increase of slow-wave activity in non-REM sleep. The combination of caffeine (15 mg/kg) and sleep deprivation caused less increase in slow-wave activity than sleep deprivation alone, indicating that caffeine may reduce the buildup of sleep pressure during waking. The results are consistent with the involvement of adenosine in the regulation of non-REM sleep.
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PMID:Effects of N6-cyclopentyladenosine and caffeine on sleep regulation in the rat. 873 4

Although adenosine receptor-based treatment of cerebral ischemia and other neurodegenerative disorders has been frequently advocated, cardiovascular side effects and an uncertain therapeutic time window of such treatment have constituted major obstacles to clinical implementation. Therefore, we have investigated the neuroprotective effects of the adenosine A1 receptor agonist adenosine amine congener (ADAC) injected after either 5 or 10 min ischemia at 100 micrograms/kg. When the drug was administered at either 6 or 12 h following 5 min forebrain ischemia, all animals were still alive on the 14th day after the occlusion. In both ADAC treated groups neuronal survival was approximately 85% vs. 50% in controls. Administration of a single dose of ADAC at times 15 min to 12 h after 10 min ischemia resulted in a significant improvement of survival in animals injected either at 15 or 30 min, or at 1, 2, or 3 h after the insult. In all 10 min ischemia groups, administration of ADAC resulted in a significant protection of neuronal morphology and preservation of microtubule associated protein 2 (MAP-2). However, postischemic Morris' water maze tests revealed full preservation of spatial memory and learning ability in animals injected at 6 h. On the other hand, the performance of gerbils treated at 12 h postischemia was indistinguishable from that of the controls. Administration of ADAC at 100 micrograms/kg in non-ischemic animals did not result in bradycardia, hypotension, or hypothermia. The data indicate that when ADAC is used postischemically, the most optimal level of protection is obtained when drugs are given at 30 min to 6 h after the insult. Although the mechanisms involved in neuroprotective effects of adenosine A1 receptor agonists require further studies, the present results demonstrate the feasibility of their clinical applications.
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PMID:Postischemic administration of adenosine amine congener (ADAC): analysis of recovery in gerbils. 898 84

1. The effects of adenosine, the adenosine analogue, 2-chloroadenosine (2-CADO), the specific adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA) and A2 receptor agonist 5'-(N-cyclopropyl) carboxamidoadenosine (CPCA), were examined against seizures induced by acute administration of pentylenetetrazole (PTZ), 60 mg kg-1, and PTZ kindled seizures, in rats. 2. Adenosine 1000 mg kg-1, i.p., 5 min pretreatment and CPA 10 mg kg-1 i.p., 60 min pretreatment, showed significant protection against acute PTZ-induced seizures while, CPCA up to 10 mg kg-1 was ineffective. The adenosine analogue 2-CADO in a dose of 5 mg kg-1 was only partially protective and on increasing the dose to 10 mg kg-1, this protection was lost. 3. Theophylline, a non specific adenosine receptor antagonist at 50 mg kg-1 and the specific adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), at 1 mg kg-1, if administered before the maximally protective doses of adenosine and CPA, completely reversed the protection afforded by them against PTZ seizures. While, pretreatment with the adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), failed to reverse the protection. 4. Adenosine and the adenosine A1 receptor agonist in doses that protected against seizures after acute PTZ administration, offered only incomplete protection when tested against PTZ kindled seizures. 5. The effects of adenosine and adenosine receptor agonists on mean arterial pressure, heart rate and rectal temperature were studied, to rule out the possibility of their systemic effects mediating the protection of PTZ seizures. All these agents produced a fall in mean arterial pressure, heart rate and hypothermia in the doses exhibiting an anticonvulsant response. While the effect on blood pressure and heart rate was immediate i.e. seen within 5 min and, maintained throughout the observation period, the development of hypothermia lagged behind the onset of hypotension and bradycardia. However, there was no correlation between haemodynamic and hypothermic response and the anticonvulsant effect. 6. The results indicate that the adenosine mediated anticonvulsant effect is via stimulation of A1 receptors. Hypotension and hypothermia do not appear to contribute to the protection observed with adenosine and the adenosine A1 receptor agonists.
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PMID:Effect of adenosine receptor modulation on pentylenetetrazole-induced seizures in rats. 911 21

We tested the hypothesis that N-[(1S, trans)-2-hydroxycyclopentyl]adenosine (GR79236), a novel adenosine A1 receptor agonist, would suppress sleep-related apnea in the rat at doses not associated with hypotension or hypothermia. Nine adult Sprague-Dawley rats were instrumented for chronic recording of sleep by electroencephalographic and electromyographic monitoring. Respirations were measured by single chamber plethysmograph, and blood pressure and heart period were transduced by a telemetric implant. Each rat was polygraphically recorded for 6 hours on four occasions in random order, with recordings for an individual animal separated by at least 3 days. Fifteen minutes prior to each recording (0945 hours) each animal received a 1 ml/kg intraperitoneal bolus injection of one of four injectates: saline (control) or 0.03 mg/kg, 0.3 mg/kg, or 3 mg/kg of GR79236. The study was a repeated-measures balanced design such that each animal was recorded exactly once for each injectate. The rate of spontaneous apneas (pauses > 2.5 seconds) was significantly reduced during all sleep stages by all doses of GR79236. At the highest dose, apnea index was reduced by over 70% in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In contrast, GR79236 had no effect on sleep stage volumes or blood pressure at any dose tested. Heart rate and core temperature were reduced only at the highest dose (3 mg/kg). We conclude that the adenosine A1 receptor agonist GR79236 significantly suppresses apnea expression in all sleep stages at doses not associated with significant changes in sleep architecture, blood pressure, heart rate, or core temperature.
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PMID:Adenosine A1 receptor agonist GR79236 suppresses apnea during all sleep stages in the rat. 998 62

Hibernation in mammalians such as hamsters is a physiological state characterized by an extreme reduction of various functions such as body temperature and metabolism. Under such severe conditions, the central nervous system (CNS) activity is maintained at a functionally responsive level. Although hibernation is an interesting behavioral state, the physiological mechanisms of the introduction to and/or the arousal from hibernation have not been clearly defined. Intracerebroventricularly (i.c.v.) injected adenosine produces hypothermia in various animals. The effect of adenosine is generated by A1-receptors and is caused by the suppression of the thermogenesis center of the posterior hypothalamus. At on ambient temperature of 5, i.c.v. injected N6-cyclohexyladenosine (CHA) adenosine A1-receptor agonist induces profound hypothermia in hamsters. Although the time course of the descent of body temperature coincided with that of entry into natural hibernation, the effect was not antagonized by 8-cyclopentyltheophyllin (CPT), an adenosine A1-receptor antagonist. However, i.c.v. injection of CPT elevated the body temperature and interrupted hibernation, albeit the deep-phase (post-entry 30 h) was unaffected. This result suggests that a different system may suppress the thermogenesis center in the deep hibernation phase. Interestingly, i.c.v. injected thyrotropin releasing hormone (TRH) elevated the body temperature in both hibernation phases in hamsters. These findings suggest that the central adenosine and TRH play important roles in thermoregulation and that the new thermogenesis system, activating in low-body temperature, is induced in naturally hibernating animals.
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PMID:[Pharmacological aspects of mammalian hibernation: central thermoregulation factors in hibernation cycle]. 1121 81

Ischemic preconditioning models have been characterized in brain, heart, and other tissues, and previous pharmacologic studies have suggested an involvement of adenosine and ATP dependent potassium (KATP) channels in such tolerance phenomena. This question was reexamined in a reproducible gerbil model in which the duration of ischemic depolarization defined the severity of preconditioning and test insults. Agents studied were glibenclamide, a blocker of KATP channels; 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an adenosine A1 receptor antagonist; and N6-cyclopentyladenosine (CPA), an A1 agonist. Intraventricular glibenclamide injections aggravated neuron damage after brief priming insults, in parallel with a dose-dependent prolongation of ischemic depolarization. However, the depolarization thresholds for ischemic neuronal injury were identical in vehicle- and glibenclamide-treated animals, and glibenclamide did not affect preconditioning when equivalent insult severity was maintained during priming insults. Neither DPCPX nor CPA had any effect on the onset or duration of depolarization after intraperitoneal injection in this model, and neither drug affected neuron damage. In the case of CPA, it was necessary to maintain temperature for 4 to 6 hours of recirculation to avoid significant confounding hypothermia. These results fail to support a direct involvement of A1 receptors or KATP channels during early stages in the development of ischemic tolerance in vivo, and emphasize the need for robust, well-controlled, and quantitative models in such studies.
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PMID:Pharmacological manipulations of ATP-dependent potassium channels and adenosine A1 receptors do not impact hippocampal ischemic preconditioning in vivo: evidence in a highly quantitative gerbil model. 1512 88


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