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)

The effects of systemic hypothermia (33.5 degrees C) on the ischemia-evoked release of the neurotransmitter amino acids, glutamate, aspartate, gamma-amino-butyric acid (GABA) and glycine into rat cerebral cortical superfusates were evaluated in the rat four vessel occlusion model. Glutamate, aspartate and GABA, but not glycine, levels were enhanced during and following a 20 min period of ischemia. However, when compared with normothermic ischemic animals, no reductions in glutamate, aspartate or GABA levels in the superfusates were apparent either prior to, during or following forebrain ischemic episodes. Indeed, the superfusate levels of aspartate and GABA were transiently increased immediately following ischemia. Glycine levels were significantly depressed, both pre- and post-ischemia, in cortical superfusates from hypothermic animals in comparison with normothermic rats.
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PMID:The effects of hypothermia on amino acid neurotransmitter release from the cerebral cortex. 167 60

The aim of the present study was to investigate if a physical dependence could be induced by chronic activation of the endogenous enkephalinergic system. We have therefore evaluated naloxone-induced withdrawal syndrome in rats after central infusion during 7 days of comparable antinociceptive doses of RB 38 A ((R,S)HONH-CO-CH2-CH(CH2C6H5)-CONH-CH(CH2C6H5)-COOH), a mixed enkephalin catabolism blocker and of the selective mu, DAGO (Tyr-D-Ala-Gly-(Me)Phe-Gly-ol) and delta, DSTBULET (Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr), opioid agonists. The responses were compared to those induced by RB 38 B ((S,S)HONH-CO-CH2-CH(CH2C6H5)-CONH-CH(CH2C6H5)-COOH), a selective inhibitor of the 24.11 neutral endopeptidase (NEP) 'enkephalinase'. DAGO induced a severe withdrawal syndrome evidenced by a large weight loss, hypothermia, jumping, mastication, teeth chattering, diarrhoea, lacrimation and salivation. In contrast, DSTBULET and RB 38 A produced only a moderate physical dependence. Only two signs were statistically different in these two groups: wet dog shakes and temperature. Chronic i.c.v. administration of DAGO, DSTBULET and RB 38 A produced a time-dependent reduction in analgesia, but 120 h after continuous infusion only RB 38 A was able to still induce a significative antinociceptive effect. The present data suggest that even in the drastic conditions used here long-term complete inhibition of enkephalin catabolism induces a weak tolerance and a moderate physical dependence, similar to that produced by delta opioid agonists. This effect was not observed after chronic selective inhibition of NEP by RB 38 B.
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PMID:Differences in physical dependence induced by selective mu or delta opioid agonists and by endogenous enkephalins protected by peptidase inhibitors. 216 53

Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and MIF-1 (Pro-Leu-Gly-NH2) can increase GABA-stimulated benzodiazepine binding in brain tissue can block the hypothermia induced by several other compounds. Since benzodiazepines can also cause hypothermia, colonic temperatures were measured in mice after administration of chlordiazepoxide (CDP) and these two brain peptides. In several experiments involving different doses and times of administration of CDP, MIF-1, and Tyr-MIF-1, there were no significant effects of the peptides in altering the reliable decrease in colonic temperature induced by the benzodiazepine. The results indicate that the interaction of Tyr-MIF-1 and MIF-1 with benzodiazepines does not involve thermoregulation.
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PMID:MIF-1 and Tyr-MIF-1 fail to alter benzodiazepine-induced hypothermia. 257 Nov 69

Short-lasting decrease in rectal temperature in mice after intraperitoneal administration of an enkephalin dimer, the so called double-enkephalin--(Tyr-D-Ala-Gly-Phe-NH)2 (D-ENK-O)--at dose 0.1, 0.5, 1, 2.5, 5, 10 and 20 mg/kg of body weight was observed. Another double-enkephalin--Tyr-D-Ala-Gly-Phe-NH-(CH2)3-HN-Phe-Gly-D-Ala-Tyr-- fai led to produce this effect. The hypothermic effect of D-ENK-O was almost completely reduced by naloxone which suggests an involvement of opiate receptors in the D-ENK-O produced hypothermia in mice.
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PMID:The effect of enkephalin dimers on body temperature in mice. 365 11

Acute intraventricular administration of human beta-endorphin (15 microgram) produced analgesia, hypothermia and catalepsy in male Sprague-Dawley rats. Injections of beta-endorphin given every 8 hr for 3 days resulted in the development of tolerance to all of the above mentioned pharmacological effects. Tolerance developed rapidly to the hypothermic effect and less rapidly to the analgesic and cataleptic effects. After the third or the fourth injection of beta-endorphin, pronounced hyperthermia, rather than hypothermia, was observed. After seven or eight injections of beta-endorphin, tolerance to the analgesic effect was complete and the cataleptic effect was reduced to 50% of the original. Daily s.c. administration of Pro-Leu-Gly-NH2 (MIF) or cyclo(Leu-Gly) (2 mg/kg each) blocked the development of tolerance to the analgesic and cataleptic effects of beta-endorphin. The hyperthermic effect of beta-endorphin in beta-endorphin-tolerant rats was partially blocked by both MIF and cyclo(Leu-Gly). Multiple injections of MIF or cyclo(Leu-Gly) did not alter beta-endorphin-induced analgesia, catalepsy and hypothermia in rats which were given repeated intraventricular injections of saline. Since MIF is a naturally occurring peptide of hypothalamic origin, these studies suggest that the hypothalamus may be an important site in regulating the pharmacological effects of chronically administered endogenous opiates.
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PMID:Inhibition of tolerance to the pharmacological effects of human beta-endorphin by prolyl-leucyl-glycinamide and cyclo(leucylglycine) in the rat. 611 70

The effects of melanotropin release inhibiting factor (Pro-Leu-Gly-NH2; MIF) and its three analogs Pro-ILeu-Gly-NHi2, Leu-Gly-NH2 (a metabolite of MIF) and cyclo (Leu-Gly) (an analog derived theoretically from MIF) on tolerance to morphine-induced hyperthermia, hypothermia and catalepsy were studied in male Sprague-Dawley rats. Subcutaneous implantation of four morphine pellets (each containing 75 mg of morphine-free base) during a 3-day period resulted in the development of tolerance to these pharmacological effects of morphine as evidenced by decreased intensity of responses to designated i.p. doses of morphine. Concurrent daily s.c. administration of each peptide, injected 24 hr apart for 3 days, resulted in blockade of tolerance to the pharmacological effects of morphine as evidenced by a greater pharmacological response in peptide plus morphine-treated rats as compared with the vehicle plus morphine-treated rats. Multiple injections of peptides did not modify morphine-induced responses in rats implanted with placebo pellets. The blockade of tolerance to morphine by these peptides was not associated with changes in the distribution of morphine in brain and plasma. These studies indicate that the following changes do not modify the inhibitory action of MIF tolerance: 1) substitution of ILeu in place of Leu in MIF; 2) cleavage of the Pro-Leu bond which gives rise to Leu-Gly-NH2; and 3) possible cyclization (diketopiperazine formation) of Leu-Gly-NH2 which yields cyclo (Leu-Gly), and that linear and cyclic peptides either derived from the hypothalamus or synthesized may provide agents to block opiate-induced tolerance.
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PMID:Structure activity relationship studies with hypothalamic peptide hormones. I. Effect of melanotropin release inhibiting factor and analogs on tolerance to morphine in the rat. 612 Feb 29

The effects of several analogs of melanotropin-release inhibiting factor (MIF, Pro-Leu-Gly-NH2) on the development of tolerance to the hyperthermic, hypothermic and cataleptic actions of morphine were investigated in male Sprague-Dawley rats. The analogs that were examined included. Pro-Gly-Gly-NH2 (I), Pro-VAl-Gly-NH2 (II), Pro-Leu-beta-Ala-NH2 (III), Pro-Leu-Gly-NHCH3 (IV), Pro-Leu-NH2 (V) and cyclo (Pro-Gly) (VI). Subcutaneous implantation of four morphine pellets (each containing 75 mg of morphine free base) during a 3-day period was used to develop tolerance to the pharmacological effects of morphine. Concurrent daily subcutaneous administration of any of the above peptides (I through VI) at a 10 mu mol/kg dose did not modify the development of tolerance to morphine-induced hyperthermia, hypothermia or catalepsy. The development of tolerance to morphine was, however, inhibited by equivalent doses of MIF. Treatment with these peptides did not alter the distribution of morphine in brain and plasma. It is concluded that the structural requirements for the inhibitory effect of MIF on the development of tolerance to morphine are very strict and that the following modifications in the structure of MIF result in the loss of activity (a) substitution of Gly or Val in place of Leu (b) replacement of Gly-NH2 with Gly-NHCH3 or beta-Ala-NH2 (c) removal of Gly, and (d) removal of Leu followed by cyclization of Pro-Gly.
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PMID:Structure activity relationship studies with hypothalamic peptide hormones III. Effect of melanotropin-release inhibiting factor and analogs on tolerance to morphine in the rat. 612 92

MIF-1 (Pro-Leu-Gly-NH2), a hypothalamic tripeptide, has been demonstrated to stimulate naloxone in antagonizing the effects of opioid peptides in a number of experimental systems including enkephalin-induced analgesia in the tail-flick assay, beta-endorphin induced hypothermia and hypomotility, deprivation-induced drinking, and analgesia in goldfish. MIF-1, however, has no effect upon the activity of enkephalins in the mouse vas deferens or enkephalin binding in the rat striatum. We have studied the interactions of MIF-1 with Leu5-enkephalin (Leu5-ENK) in the conscious, chronically instrumented dog. Although naloxone inhibits both the elevations of heart rate and blood pressure produced by IV Leu5-ENK in the conscious state and the depressions in these variables produced by Leu5-ENK after pentobarbital anesthesia, MIF-1 has no effect upon the Leu5-ENK response in either state. However, both naloxone and MIF-1 seem to raise mean arterial pressure in the conscious dog. These results indicate that MIF-1 does not act like naloxone in antagonizing the peripheral effects of Leu5-ENK and lend further support to the existence of mechanistic differences among opiate-mediated behavior, analgesia, and cardiovascular activity.
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PMID:MIF-1 does not act like naloxone in antagonizing the cardiovascular activity of leucine-enkephalin in the conscious dog. 613 37

Cyclo(Leu-Gly) (cLG), a diketopiperazine analog of Pro-Leu-Gly-NH2 (MIF), affects a number of physiological and behavioral responses to the endogenous neurotransmitter, dopamine (DA). In the present series of experiments, the effect of in vivo administration of cLG (8 mg/kg) was investigated five days following subcutaneous administration. It was found that cLG administration of cLG (8 mg/kg) was investigated five days following subcutaneous administration. It was found that cLG administration caused a supersensitive behavioral response, measured by increased stereotypic sniffing, to the DA agonist, apomorphine (APO). At the same time, an increase was found in the affinity for dopamine (DA), as measured by dopamine inhibition of 3H-spiroperidol binding to D-2 DA receptors in striatum (nigro-striatal DA tract). In contrast, the same peptide treatment caused a subsensitive physiological response to APO-induced hypothermia, concomitant with a decrease in affinity for dopamine, as measured by DA inhibition of 3H-spiroperidol binding to D-2 DA receptors in hypothalamus (incerto-hypothalamic DA tract). These results suggest that a single neuromodulatory agent, the peptide cLG, can elicit diametrically opposite effects on D-2 DA receptors and on the corresponding physiological endpoints in two different brain areas.
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PMID:Cyclo(Leu-Gly) has opposite effects on D-2 dopamine receptors in different brain areas. 623 32

Neurotensin (NT), an endogenous tridecapeptide, produces significant hypothermia after intracisternal (i.c.) or intracerebroventricular (i.c.v.) administration in microgram quantities in a variety of laboratory animals. The present study sought to clarify the mechanism of the hypothermic action by utilizing pharmacological treatments which alter the function of brain neurotransmitter systems. Pretreatment of rats with anti-muscarinic (atropine), anti-noradrenergic (propranolol, a beta-blocker; phenoxybenzamine, an alpha-blocker) or anti-opiate (naloxone) agents did not significantly alter NT-induced hypothermia. Similarly depletion of brain serotonin (5-HT) with parachlorophenylalanine did not affect NT-induced hypothermia. However, depletion of brain catecholamine content with 6-hydroxydopamine resulted in a significant potentiation of NT-induced hypothermia as did pretreatment with haloperidol, a dopamine (DA) receptor antagonist. Furthermore, in rats with selective depletions of brain DA, but not norepinephrine (NE), NT-induced hypothermia was significantly augmented. Thus an interaction between brain DA systems and NT appears likely. These data indicate that NT-induced hypothermia is not dependent on intact functional activity of NE, 5-HT, muscarinic ACh or endogenous opiate systems but suggests interactions between brain DA circuits and NT. In other experiments, NT-induced hypothermia was found to be antagonized significantly by i.c. injection of thyrotropin-releasing hormone (TRH), but not by pretreatment with L-triiodothyronine. Another endogenous tripeptide (Pro--Leu--Gly--NH2, MIF-I) had no effect. Thyroidectomy (THX) significantly potentiated NT-induced hypothermia; NT administered i.c. significantly reduced the high serum TSH levels of THX rats. Thus, NT and TRH, two endogenous peptides, appear to be antagonists in certain systems.
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PMID:Neurotensin-induced hypothermia: evidence for an interaction with dopaminergic systems and the hypothalamic--pituitary--thyroid axis. 644 51


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