Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q17RS7 (Gen)
 130,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a screening survey for hypothermia carried out amongst the elderly population of an island in the Orkneys, in which a 96 per cent response rate was obtained, oral temperatures were recorded using standard and low-reading thermometers. Out of 77 patients who entered the survey, only three had an oral temperature of 37 degrees C or higher. Six patients (eight per cent) had a temperature of 35 degrees C or lower, and these, depending on diagnostic criteria, could be considered to be suffering from hypothermia. A low body temperature was unsuspected in all six.
J R Coll Gen Pract 1975 Sep
PMID:Screening for hypothermia in Orkney. 118 20

The effect of repeated treatment (5 and 10 mg/kg, po, twice daily, 14 days) with sertraline and citalopram (antidepressants which selectively inhibit the reuptake of 5-hydroxytryptamine (5-HT)) on the responsiveness of different 5-HT receptors to their agonists, was examined in rats and mice. Sertraline and citalopram (both at a dose 5 and 10 mg/kg) antagonized (the first one more potently) the hypothermia induced in mice by 8-OH-DPAT (a 5-HT1A agonist), but not the behavioural syndrome induced in rats by this substance. The m-chlorophenylpiperazine-induced hypothermia in mice (a 5-HT1B effect) was increased by sertraline and citalopram (only in a dose of 10 mg/kg). Both antidepressants, given repeatedly (as well acutely) attenuated exploratory hypoactivity induced in rats by m-chlorophenylpiperazine (a 5-HT1C effect). L-5-HTP-induced head twitches in mice (5-HT2 effect) were antagonized dose-dependently by both repeated sertraline and citalopram. Both antidepressants (citalopram only in higher dose) reduced the fenfluramine-induced hyperthermia in rats (5-HT2 effect). The results indicate that sertraline and citalopram given repeatedly decrease the responsiveness of 5-HT1A (presynaptic) and 5-HT2 receptors but increase the responsiveness of 5-HT1B receptors to respective agonists.
J Neural Transm Gen Sect 1992
PMID:Effects of sertraline and citalopram given repeatedly on the responsiveness of 5-HT receptor subpopulations. 138 65

1. The effects of two anaesthetics, sodium pentobarbital and urethane, and the effects of anaesthesia-associated hypothermia on acid-base status and blood gases were studied in rats without assisted ventilation. 2. Manipulation of conscious rats produces a progressive increase in arterial lactate associated with slight hyperventilation. 3. Sodium pentobarbital anaesthesia produces mild respiratory acidosis accompanied by increase in lactate arterial values. Urethane anaesthesia leads to partially compensated metabolic acidosis. 4. Hypothermia reduces metabolic acidosis and hypercapnia induced by sodium pentobarbital anaesthesia. No difference between hypothermic and normothermic values was observed in urethane anaesthesia.
Gen Pharmacol 1992 Jul
PMID:Differential effects of hypothermia upon blood acid-base state and blood gases in sodium pentobarbital and urethane anaesthetised rats. 139 74

1. Prazosin (PRA) was used in febrile (LPS; 1 mcg/kg; i.v.) and normothermic rabbits at ambient temperatures (Ta) of 5, 19 and 28 degrees C. This drug was given i.v. in the form of an infusion at a rate of 0.75 mg/kg/3 hr. 2. In normothermic animals, PRA produced significant hypothermia mainly at Ta of 5 and 19 degrees C. In a cold environment, the hypothermic effect of PRA was associated with inhibition of metabolic rate and evaporative heat loss. 3. Infusion of this drug significantly prevented the LPS-induced fever in all experimental conditions. In the cold environment, a drop in body temperature was correlated with an inhibition of metabolic rate; in the thermoneutral environment, antipyresis was associated with an increase in heat dissipation from the ear-skin area; in the hot environment, the correlation between antipyresis and mechanisms of heat dissipation was much less clear. 4. The possible action of PRA on the effector part of the central thermoregulatory system is discussed.
Gen Pharmacol 1992 Nov
PMID:Do central mechanisms participate in the thermoregulatory activity of prazosin? 148 22

Hormonal modulation of neurotransmission emerged as a concept from the recognition that adrenocortical steroids exert profound effects at the level of receptors, G-proteins and effector units. G-proteins, a family of guanine nucleotide binding regulatory components that couple neurotransmitter receptors to various types of intracellular effector systems, appear to be a key target of glucocorticoid (GC) action in the CNS. It is thought that Gs/Gi mediates stimulation/inhibition of adenylate cyclase (AC system), which forms cyclic AMP as second messenger, while receptors stimulating phospholipase C do so through Go to produce two second messengers, inositol 1,4,5-triphosphate and diacylglycerol (PI system). Recent evidence suggests that GC increase Gs alpha-and decrease Gi alpha-protein subunit expression without affecting Go alpha. Activation of central pre- and postsynaptic 5-HT1A receptors which are linked to the Gi-AC complex, induces hypothermia and ACTH/cortisol release in rodents and humans. Compared with controls, patients with a major depressive disorder exhibit increased basal cortisol secretion associated with decreased hypothermic and ACTH/cortisol responses. The attenuated neuroendocrine and thermoregulatory response to 5-HT1A receptor activation may reflect a GC-dependent feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) system and subsensitivity of the presynaptic 5-HT1A-Gi-AC complex function. Differential regulation of 5-HT1A and 5-HT2 function leading to a relative 5-HT2-Go-PI complex supersensitivity may maintain HPA hyperactivity during the course of depression. These findings corroborate recent reports that GC, via GC-GC receptor (GR) complex activated promotion of gene transcription, modify the expression 5-HT1A-coupled Gi (but not 5-HT2-coupled Go) resulting in altered sensitivity of 5-HT1A-mediated signal transduction and further support the hypothesis of a differential regulation of 5-HT1A and 5-HT2 receptor function and a GC-GR/5-HT1A-G-protein--effector system-related abnormality in depression.
J Neural Transm Gen Sect 1991
PMID:The 5-HT receptor--G-protein--effector system complex in depression. I. Effect of glucocorticoids. 164 69

1. Intraperitoneal (i.p.) injection to restrained rats of GABA (250-1000 mg/kg) or the GABAA-receptor agonist muscimol (0.05-1 mg/kg) induced a dose-dependent decrease in body temperature (BT). 2. Intraperitoneal injection of low doses of the GABAB-receptor agonist (+/-)-baclofen (1-10 mg/kg) did not significantly affect BT. However, baclofen, at high doses (30 mg/kg), produced an increase in BT. 3. Pretreatment with either bicuculline (3 mg/kg) or naloxone (1 mg/kg) did not significantly modify the hypothermic response observed with GABA or muscimol, except for the high dose of GABA (1000 mg/kg) which was potentiated by bicuculline pretreatment. 4. Indomethacin pretreatment (5 mg/kg) significantly antagonized the hypothermia induced by GABA and muscimol. 5. Injection of baclofen alone (1 mg/kg) did not significantly affect BT, but in presence of the GABAA antagonist bicuculline, baclofen significantly decreased BT. 6. Baclofen-induced hyperthermia appear to be via prostaglandin and opioid mechanisms since both indomethacin and naloxone abolish this effect. 7. The hypothermia induced by GABA-agonists appears to be due to simultaneous activation of GABAA and GABAB receptors, while the hyperthermic effect of baclofen appears to be due to stimulation of GABAB receptors. 8. The present results suggest that involvement of prostaglandins in the effects of GABA, muscimol and baclofen, while endogenous opiates seem to be implicated only in baclofen induced hyperthermia. 9. It can be concluded that GABA may be involved in the control of BT through GABAA and GABAB receptors.
Gen Pharmacol 1991
PMID:Opioid and prostaglandin mechanisms involved in the effects of GABAergic drugs on body temperature. 164 43

1. Administration of bromocriptine (0.1-2.5 mg/kg, i.p.) to mice produced hypothermia. 2. Pretreatment with the alpha 1-adrenoceptor blocker, prazosin (2.0 mg/kg, i.p.) or the alpha 2-adrenoceptor antagonist yohimbine (2.5 mg/kg, i.p.) had no effect on this response. 3. The inhibitor of catecholamine synthesis, alpha-methyl-p-tyrosine, and the muscarinic antagonist, atropine (10 mg/kg, i.p.) failed to alter the hypothermia. 4. Pretreatment with the dopamine (DA) receptor antagonists haloperidol (0.02 mg/kg, i.p.) or cis-flupenthixol (0.01 mg/kg, i.p.) completely blocked this response while trans-flupenthixol (0.05 mg/kg, i.p.) was inactive. 5. Depletion of 5-HT in the brain by p-chlorophenylalanine reduced the hypothermic response. 6. Similarly, pretreatment with the serotonergic (5-HT) receptor blocker ketanserin (1 mg/kg, i.p.) attenuated the hypothermia and at a dose of 2 mg/kg (i.p.) it completely blocked the hypothermic response. 7. Methysergide (5 mg/kg, i.p.) was also effective in antagonizing the hypothermia. 8. It was concluded that both DA and 5-HT mechanisms are involved in bromocriptine-induced hypothermia in mice.
Gen Pharmacol 1991
PMID:Bromocriptine-induced hypothermia in Balb/C mice: its possible mechanism of action. 165 Dec 67

To evaluate 5-hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder, we examined hypothermic, neuroendocrine, and behavioral responses to the selective 5-hydroxytryptamine1A receptor ligand ipsapirone in patients with primary obsessive-compulsive disorder and healthy controls. Twelve patients and 22 controls received a single dose of ipsapirone, 0.3 mg/kg, or placebo under double-blind, random assignment conditions. Ipsapirone induced hypothermia and release of corticotropin and cortisol but had no effect on behavior, including obsessive or compulsive symptoms. Thermoregulatory and neuroendocrine responses to ipsapirone were not consistently different between healthy controls and patients with obsessive-compulsive disorder. These results provide no direct support for the hypothesis that a serotonergic dysfunction related to 5-hydroxytryptamine1A receptors may be linked to the pathophysiologic characteristics of obsessive-compulsive disorder and point to the need for the evaluation of other 5-hydroxytryptamine receptor subtypes. Future studies of the responsivity of 5-hydroxytryptamine1A receptors to direct-acting ligands, such as ipsapirone, should facilitate assessment of the integrity of the 5-hydroxytryptamine system and its involvement in antiobsessional drug effects.
Arch Gen Psychiatry 1991 Jun
PMID:5-Hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder. Comparison of patients and controls. 167 53

Buspirone, a putative serotonin (5-HT)1A partial agonist, did not produce hypothermia in 17 normal volunteers in a placebo controlled, single blind study. Thus, buspirone may be a weaker agonist at those 5-HT1A receptors which mediate hypothermia compared to ipsapirone or gepirone, two other 5-HT1A partial agonists which have been reported to produce hypothermia by a 5-HT1A-mediated mechanism.
J Neural Transm Gen Sect 1991
PMID:Buspirone does not produce a 5-HT1A-mediated decrease in temperature in man. 175 Oct 30

Our earlier studies showed that dihydropyridine calcium channel antagonists have some central pharmacological effects. Flunarizine is considered to be a calcium channel antagonist; therefore this study was aimed at investigating the effect of flunarizine (given in single doses of 5, 10 and 20 mg/kg p.o.) in behavioural models in which calcium channel antagonists of the dihydropyridine type were previously studied. Flunarizine inhibited the apomorphine-induced stereotypy and yawning behaviour in rats. It decreased the hypothermia induced by a low dose of apomorphine in mice, but not that one induced by high dose of it. The quinpirole-induced hypothermia was also reduced. In the tests used for evaluation of the effect on the serotonergic system, flunarizine decreased the 5-HTP-induced head twitches and partly antagonized the fenfluramine- and quipazine-induced hyperthermias (at a high ambient temperature). In the forced swimming test flunarizine was inactive in mice and rats. The obtained results indicate that flunarizine exerts central antagonistic effects on the dopaminergic and serotonergic systems and has no antidepressant activity. Flunarizine differs from calcium channel antagonists of the dihydropyridine type, which have no dopamine-antagonistic activity and show anti-depressant-like properties.
J Neural Transm Gen Sect 1991
PMID:Some central pharmacological effects of the calcium channel antagonist flunarizine. 203 9


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