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)

1. Amphetamine-induced hypothermia in mice is facilitated by dopaminergic stimulation and 5-hydroxytryptaminergic inhibition. The present study was designed to investigate: (a) the involvement of other neuronal systems, such as the gamma-aminobutyric acid (GABA), the opioid and the cholecystokinin (CCK-8) systems; (b) the possible contribution of hydroxylated metabolites of amphetamine to the hypothermia; (c) the capacity of dopamine itself to induce hypothermia and its mechanisms, in order to clarify the resistance of amphetamine-induced hypothermia to certain neuroleptics. 2. Pretreatment with the GABA antagonists, bicuculline and picrotoxin, did not inhibit amphetamine-induced hypothermia. The GABAB agonist, baclofen (2.5 mg kg-1, i.p.) potentiated this hypothermia, whereas the GABAA agonist, muscimol, did not. gamma-Butyrolactone (GBL) (40 mg kg-1, i.p.) and the neuropeptide CCK-8 (0.04 mg kg-1, i.p.) also induced potentiation. The opioid antagonist, naloxone, was without effect. 3. Dopamine itself (3, 9, 16 and 27 micrograms, i.c.v.) induced less hypothermia than the same doses of amphetamine. Sulpiride did not block dopamine-induced hypothermia, but pimozide (4 mg kg-1, i.p.), cis(z)flupentixol (0.25 mg kg-1, i.p.) and haloperidol (5 micrograms, i.c.v.) did. The direct dopamine receptor agonist, apomorphine, did not alter the hypothermia. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the inhibitor of 5-HT synthesis, p-chlorophenylalanine (PCPA), modified dopamine-induced hypothermia. Fluoxetine, an inhibitor of 5-HT reuptake, had no effect, whereas quipazine (6 mg kg-1, i.p.), a 5-HT agonist, totally prevented the hypothermia. Hypothermia was unaffected by pretreatment with CCK-8. 4. These data indicate that the hypothermia induced by amphetamine involves not only dopaminergic and 5-hydroxytryptaminergic systems which are functionally antagonistic, but is also facilitated by direct or indirect GABA and CCK-8 receptor stimulation. This facilitation could result, in part, from modulation of dopaminergic neurotransmission. This may explain the apparent resistance of amphetamineinduced hypothermia to some neuroleptics, while dopamine-induced hypothermia is not resistant. The possible action of hydroxylated metabolites of amphetamine may also help to explain these differences.
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PMID:Facilitation of amphetamine-induced hypothermia in mice by GABA agonists and CCK-8. 185 28

The effects of intracerebroventricular (icv) vasoactive intestinal polypeptide (VIP), secretin, glucagon, and cholecystokinin-octapeptide (CCK-8) on the thermoregulatory and cardiovascular systems were studied in conscious rats. The icv injection of VIP at a dose of 10 micrograms produced hyperthermia with an increase in the positive difference between the interscapular brown adipose tissue (BAT) and colonic temperatures (TBAT-Tco), but had little effect on nonevaporative heat loss. Mean arterial blood pressure and heart rate increased following the icv VIP. The results were consistent at ambient temperatures (Ta) of 18, 23, and 28 degrees C. The icv injection of secretin at doses of 1 and 10 micrograms at Ta of 23 degrees C produced hypothermia with a decrease in (TBAT-Tco) and elevated blood pressure without any change in heart rate. The 10 micrograms of icv glucagon had no effect on the thermoregulatory and cardiovascular systems. The large dose of icv CCK-8 (10 micrograms) induced persistent hyperthermia. Nonsulfated-form CCK-8 and CCK-tetrapeptide, however, were ineffective on all variables measured. These results indicate that the central VIP activates BAT thermogenesis and induces hyperthermia, but has a minimum effect on nonevaporative heat loss. Although VIP, secretin, and glucagon have similarities in terms of chemical structure, their effects on body temperature, BAT thermogenesis, and the cardiovascular system are quite different.
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PMID:Changes in brown adipose tissue metabolism following intraventricular vasoactive intestinal peptide and other gastrointestinal peptides in rats. 279 18

Subcutaneous injection of cholecystokinin octapeptide (CCK-8) (0.005-1.25 mg/kg) elicited dose-dependent hypothermia in rats. The threshold of the response was between 0.01 and 0.05 mg/kg and the dose-response curve levelled off at doses larger than 0.2-0.5 mg/kg. Warm and cold ambient temperatures decreased and increased the response, respectively. Pretreatment with capsaicin, morphine, naloxone, atropine, haloperidol or propranolol did not affect the response to CCK-8, whereas pretreatment with phenoxybenzamine and a large dose of proglumide, an antagonist for CCK-receptors, attenuated the hypothermia. It seems that neither capsaicin-sensitive thermal and non-thermal afferents, nor opiate mechanisms are involved in the response, but alpha-adrenoceptors might be of some importance in the hypothermia. Non-sulphated-CCK-8, the C-terminal tetrapeptide and hexapeptide, [D-Ala4]-CCK-8 and [D-Met6]-CCK-8 were ineffective. Chronic treatment with CCK-8 resulted in the development of tolerance to the thermoregulatory effect, while the hypothermic responses to apomorphine and capsaicin were not affected. It seems that the tolerance cannot be attributed to conditioned homeostatic reactions.
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PMID:Cholecystokinin-octapeptide-induced hypothermia in rats: dose-effect and structure-effect relationships, effect of ambient temperature, pharmacological interactions and tolerance. 358 28

Rats were chronically implanted with a hypothalamic cannula to allow chemical stimulation of the hypothalamus on the conscious animals in repeated experiments. Direct administration of cholecystokinin octapeptide (CCK-8) (20-60 ng) into the preoptic anterior hypothalamic area caused a dose-related fall in rectal temperature at ambient temperatures of 8 degrees C and 22 degrees C. The hypothermia induced by CCK-8 was produced by a decrease in metabolism at an ambient temperature of 8 degrees C, whereas at 22 degrees C, it was caused by both a decrease in metabolism and an increase in cutaneous temperature. However, at an ambient temperature of 30 degrees C, intrahypothalamic administration of CCK-8 caused an insignificant change in thermoregulatory responses. Furthermore, neither intrahypothalamic injection of 0.9% saline nor intraperitoneal injection of CCK-8 (60 ng) had any effect on thermoregulatory responses at the ambient temperatures of 8 degrees-30 degrees C studied. Under urethane anaesthesia, 59 single neurons in the preoptic anterior hypothalamic area were examined in 29 rats. Each animal was subjected to scrotal warming or cooling and to the administration of CCK-8. Microiontophoretic application of CCK-8 resulted in inhibition of the majority (75%) of cold-responsive neurons as well as excitation of the majority (77.8%) of warm-responsive neurons recorded in the preoptic anterior hypothalamic area. However, the majority (69%) of thermally unresponsive cells were not affected by CCK-8 application. The data indicate that CCK-8, when administered intrahypothalamically, excites warm-responsive neurons and inhibits cold-responsive neurons within the preoptic anterior hypothalamic area to induce hypothermia by promoting an increase in heat loss and a decrease in heat production.
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PMID:Effects of cholecystokinin octapeptide on thermoregulatory responses and hypothalamic neuronal activity in the rat. 399 Aug 27

Proglumide has been reported to antagonize sulfated cholecystokinin octapeptide (CCK-8) in peripheral tissue and in neurophysiological single unit preparations. The present studies attempt to extend this reported antagonism to several actions of CCK-8 in mice in vivo. For comparison with proglumide, the antagonist activity of naloxone against CCK-8 has also been evaluated. Proglumide (150 mg/kg) antagonizes hot plate latency elevations produced by a moderate (0.17 mg/kg s.c.) dose of CCK-8, but not that by a higher (1.0 mg/kg) dose. The effects of intracerebroventricularly (i.c.v.) administered CCK-8 (0.3 micrograms) are also blocked by proglumide i.p. or i.c.v. Naloxone (0.5 mg/kg s.c.) significantly antagonizes the elevated hot plate latencies induced by CCK-8 i.c.v. (3.0 micrograms) and s.c. (3.0 mg/kg). Proglumide antagonizes the motor activity suppressant effects of CCK-8, but only at a high proglumide dose (150 mg/kg i.p.) and low CCK-8 doses. Naloxone (3.0 mg/kg) is not effective against CCK-8 in motor activity. The hypothermia induced by CCK-8 cannot be antagonized either by proglumide at doses up to 150 mg/kg i.p. or by naloxone at doses up to 3.0 mg/kg s.c. In vivo, proglumide may be considered as a weak antagonist of CCK-8 and the possibility exists that various actions of CCK-8 may be differentiated by their relative responsiveness to proglumide-induced antagonism.
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PMID:Differential antagonism by proglumide of various CCK-mediated effects in mice. 408 Jul 8

Cholecystokinin-octapeptide (CCK-8) was shown to cause hypothermia after intracerebroventricular administration in the rat, and the hypothermic effect of CCK-8 was antagonized by simultaneous injection of TRH.
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PMID:Cholecystokinin-induced hypothermia in the rat. 625 73

Cholecystokinin octapeptide (CCK-8), ceruletide (caerulein, CER) and 10 analogues of ceruletide, were studied in mice for antagonism of the tremors induced by harmine (5 mg/kg, s.c.), ibogaine (20 mg/kg, s.c.) and oxotremorine (0.2 mg/kg, s.c.). The following reference drugs were tested for comparison: prolyl-leucylglycine amide (MIF), atropine, haloperidol, biperiden, ethopropazine, trihexyphenidyl, methixene and clonazepam. All treatments were subcutaneous, the antagonists being given 10 min (in some trials 30 min) before the tremorogen. Tremorolytic potency (ED50) was calculated from dose-response curves. Against the tremors induced by either harmine or ibogaine, CCK-8 and ceruletide, as well as many of the analogues of ceruletide had greater tremorolytic potency than the reference drugs. Against oxotremorine, however, ceruletide and its most potent analogue, Nle8-CER (other analogues were not tested) were inactive and MIF showed very little effectiveness. Additional experiments on hypothermia and sedation as well as evaluation of previous studies on other central actions suggested that the tremorolytic effect of CCK-like peptides is independent of other central effects. The CCK-like peptides may play a physiological role in the regulation of extrapyramidal motor activity.
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PMID:Cholecystokinin octapeptide (CCK-8), ceruletide and analogues of ceruletide: effects on tremors induced by oxotremorine, harmine and ibogaine. A comparison with prolyl-leucylglycine amide (MIF), anti-Parkinsonian drugs and clonazepam. 631 Apr 34

The C-terminal octapeptide of cholecystokinin (CCK-8) injected into the lateral ventricle of rats produced a lowering of body temperature. CCK-8 potentiated pentobarbital-induced hypothermia, but not the ethanol one. Thyrotropin releasing hormone (TRH) and prostaglandin E2 (PGE2) antagonized the hypothermic effect of CCK-8. Non-sulfated CCK-8 was ineffective in lowering body temperature, indicating that sulfated tyrosine in the CCK molecule is indispensable for its hypothermic action. Caerulein was found to possess rather less activity compared with CCK-8.
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PMID:Effect of cholecystokinin octapeptide on body temperature in the rat. 680 79

1. The hydroxylated metabolites of amphetamine, p-hydroxyamphetamine (p-OHA) and p-hydroxynorephedrine (p-OHN), were administered intracerebroventricularly in mice in order to evaluate their ability to elicit hypothermia. 2. Intracerebroventricular (i.c.v.) administration of p-OHA and p-OHN (1, 3 and 9 micrograms/mouse) induced maximal hypothermia 30 min after injection. p-OHA and p-OHN (9 micrograms, i.c.v.) produced maximal decreases in rectal temperature of -6.48 +/- 0.44 degrees C and -3.82 +/- 0.42 degrees C, respectively. Both metabolites are more effective than amphetamine (at 9 micrograms, i.c.v., -3.32 +/- 0.75 degrees C). 3. Pretreatment with haloperidol (5 micrograms, i.c.v.) suppressed the fall in temperature produced by p-OHA (3 micrograms, i.c.v.) and reduced that produced by p-OHN (3 micrograms, i.c.v.), respectively. The selective dopaminergic D1 receptor antagonist, SCH 23390, and the D2 receptor antagonists, sultopride and metoclopramide, were without effect on the hypothermia induced by either metabolite. Similarly, amphetamine-induced hypothermia was only inhibited by haloperidol. Apomorphine (0.1 mg kg-1, i.p.) did not potentiate the hypothermia induced by either metabolite, whereas the selective dopaminergic D2 agonist, quinpirole (0.2 mg kg-1, i.p.) did. Amphetamine-induced hypothermia was potentiated by apomorphine and quinpirole. 4. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the 5-HT receptor agonist, quipazine, modified metabolite-induced hypothermia. In contrast, amphetamine-induced hypothermia was affected by these 5-HT drugs. 5. The neuropeptide CCK-8 (0.04 mg kg-1, i.p.) and gamma-butyrolactone (40 mg kg-1, i.p.) potentiated the hypothermia produced by amphetamine and its metabolites. Conversely, desipramine (20 mg kg-1, i.p.) antagonized it.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of hydroxylated metabolites in amphetamine-induced hypothermia in mice. 809 41

We examined the effects of intracerebroventricular (i.c.v.) injections of cholecystokinin-octapeptide (CCK-8) and somatostatin (SST) and the interactions of these neuropeptides with the selective opioid antagonists, CTAP (mu) and nor-BNI (kappa) and the mu-agonist, PL017, on body temperature (Tb) of the rat at normal ambient temperature (21 +/- 0.5 degrees C). CCK-8 produced short-lasting (15-60 min), dose-related increases in Tb in a dose range of 20 to 900 ng but did not change the Tb at lower doses (0.1-2 ng). Lower doses of SST (1 and 2 micrograms) produced hyperthermia (30-60 min) and a higher dose of SST (10 micrograms) caused hypothermia (30-45 min). PL017 (1 microgram, i.c.v.), alone and in combination with CCK-8, produced hyperthermia. The CCK-8 (300 ng)-induced hyperthermia was blocked by pretreatment of rats with CTAP (1 microgram, i.c.v.), suggesting that the higher doses of CCK-8 increase Tb through the interaction with mu-receptors or the enhancement of release of endogenous opioids acting on the mu-receptor. The hyperthermia elicited by a lower dose of SST (1 microgram) was prevented by pretreatment with CTAP but not with nor-BNI (1 microgram, i.c.v.). Pretreatment with nor-BNI blocked the higher dose (10 micrograms) of SST-induced hypothermia. PL017 or CTAP did not prevent the hypothermic effect of that dose of SST. These results indicate that a lower dose of SST (1 microgram) stimulates the mu-receptor (directly or indirectly) and a higher dose (10 micrograms) interacts with the kappa-receptor in regulation of Tb. Thus, the effects of both CCK-8 and SST on Tb appear to involve the endogenous opioid system.
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PMID:Interaction of cholecystokinin and somatostatin with a selective mu-opioid agonist and mu- and kappa-antagonists in thermoregulation. 903 4


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