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 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

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

(D-ala2)-methionine-enkephalinamide (DAME) was injected into the third cerebral ventricle of unrestrained cats. At ambient temperature (Ta) = 22 degrees C, 3.1-50 micrograms caused dose-related hyperthermias. As dosage was increased, the hyperthermias diminished and in some cats hypothermia developed. Hyperthermia was not due to pyrogenic contamination or prostaglandin synthesis since it was not altered by pretreatment with a large IV dose of indomethacin. However, pretreatment with naloxone did cause a dose-related reduction in the hyperthermia. A low dose of DAME (12.5 micrograms) also caused hyperthermia at Ta = 4 and 32 degrees C, indicative of an increase in the level about which body temperature was regulated. On the other hand, a dose of 200 micrograms, which caused hyperthermia Ta = 22 and 32 degrees C, usually caused hypothermia at Ta = 4 degrees C, perhaps due to impairment of thermoregulatory control mechanisms. The response to DAME in the cold was reduced by naloxone pretreatment or reversed by subsequent injection of naloxone. Differences in hyperthermic patterns over a range of TaS and the lack of hypothermogenic action of morphine indicate that DAME alters thermoregulation in the cat by acting on morphine-insensitive, but naloxone-sensitive receptors. Central injection of beta-endorphin (5-50 micrograms) caused a dose-related hyperthermia. (Des-tyr1)-leucine-enkephalin (10-250 micrograms) was weakly hyperthermogenic, and kyotorphin (500 micrograms) did not consistently alter body temperature.
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PMID:Thermoregulatory effects of (D-ala2)-methionine-enkephalinamide in the cat. Evidence for multiple naloxone-sensitive opioid receptors. 625 Jun 78

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

Spontaneously hypertensive rats exhibited dopamine receptor supersensitivity as evidenced by a greater hypothermic response to apomorphine in comparison with normotensive Wistar-Kyoto rats. A single injection of cyclo(Leu-Gly) given prior to apomorphine administration did no alter apomorphine induced hypothermia in either the normotensive or the hypertensive rats. Chronic administration of cyclo(Leu-Gly) for 7 days did not affect apomorphine response in normotensive rats, but blocked the exaggerated response to apomorphine in the hypertensive rats. These studies suggest that cyclo(Leu-Gly) interacts with the dopamine receptors and that the central dopamine receptors may play a role in the pathophysiology of hypertension.
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PMID:Effect of cyclo(Leu-Gly) on the supersensitivity of dopamine receptors in spontaneously hypertensive rats. 684 87

The effects of intracerebroventricular (ICV) administration of two synthetic enkephalinamides, D-Ala2-Met5-enkephalinamide and D-Met2-Pro5-enkephalinamide, were compared with those of morphine on abstinence responses in morphine dependent mice. Mice were rendered dependent by morphine pellet implantation for three days. When administered six hours after pellet removal, both enkephalinamides and morphine reversed the naloxone-induced abstinence jumping response. On a molar basis, D-Met2-Pro5-enkephalinamide was the most potent compound and morphine was the least potent. Thus, substitution of D-Methionine in the two-position and prolineamide in five-position of the naturally occurring enkephalins, methionine- and leucine-enkephalin resulted in potent compound. The enkephalinamides and morphine also prevented hypothermia when injected immediately after or six hours after morphine withdrawal (pellet removal).
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PMID:Comparative effects of synthetic enkephalinamides and morphine on abstinence responses in morphine-dependent mice. 719 Mar

The neurohypophyseal hormone, arginine vasopressin (AVP), was previously shown to prolong the duration of ethanol tolerance in mice. Since drug tolerance and certain memory-related processes are examples of CNS adaptation, these phenomena have been proposed to share underlying mechanisms. We investigated the effects on ethanol tolerance of two other neurohypophyseal peptides, both of which modulate memory consolidation or retrieval of information. (Des-9-glycinamide, 8-lysine) vasopressin (DGLVP), like AVP, maintained ethanol tolerance in C57Bl mice, while cyclo(Leu-Gly) (cLG), at an equimolar dose, was ineffective. Thus, various neurohypophyseal peptides may differentially influence CNS adaptive phenomena. Direct peptide effects on ethanol-induced hypothermia and "sleep time," the parameters used to evaluate ethanol tolerance, were also determined. AVP per se caused hypothermia in mice, but neither AVP nor cLG affected ethanol-induced hypothermia. Both peptides, however, increased "sleep time" after acute ethanol administration. Although these direct peptide-ethanol interactions do not account for the observed peptide effects on tolerance, the findings emphasize the importance of using several parameters to assess ethanol tolerance.
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PMID:Neurohypophyseal peptide influences on ethanol tolerance and acute effects of ethanol. 724 29

The intensity of labelled leucine penetration from the blood-circulating system to the tissues and its incorporation into proteins of some organs of gophers have been studied under hibernation and hypothermia. It is shown that, in spite of the low temperature of the gopher body under hibernation, the intensity of amino acids transfer from the blood to the tissue was approximately the same as in active state. But the rate of proteins synthesis under hibernation considerably decreases though it is not completely stopped. Under artificial hypothermia of the mammals the transition of amino acids from the blood to the tissue is considerably hampered. Under these conditions the incorporation of labelled amino acids is completely stopped.
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PMID:[Amino acid transport and protein synthesis in ground squirrels during hibernation and artificial hypothermia]. 804 77

Protein synthesis, measured as [14C]-leucine incorporation into proteins, was studied in the normothermic rat brain following 15 min of transient cerebral ischaemia and 1 h, 24 h and 48 h of recirculation, and in the hypothermic (33 degrees C) brain following 1 h and 48 h of recirculation. Ischaemia was induced by bilateral common carotid occlusion combined with hypotension. Following normothermic ischaemia, incorporation of [14C]-leucine was depressed by 40-80% at 1 h of recirculation in all brain regions studied. At 48 h postischaemia, incorporation returned to normal or above normal levels in the inner layers of neocortex, the CA3 region, the striatum and the dentate gyrus, while in the outer layers of neocortex and in the hippocampal CA1 region the incorporation was persistently decreased by 26% and 40% respectively. At 24 and 48 h postischaemia, protein synthesis in the CA1 region and the striatum could be attributed to proliferating microglia. Intra-ischaemic hypothermia ameliorated the persistent depression of protein synthesis in the CA1 region at 48 h postischaemia, and a two-fold increase compared to the normothermic group was observed both in the CA1 region and the striatum. In the cortex, eucaryotic initiation factor 2 activity transiently decreased at 30 min postischaemia. In animals subjected to intra-ischaemic hypothermia, the eucaryotic initiation factor 2 activity was reduced by 50% of control at 30 min of recirculation compared with 77% in normothermic animals. We conclude that the postischaemic depression of protein synthesis is in part caused by a decrease in eucaryotic initiation factor 2 activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postischaemic changes in protein synthesis in the rat brain: effects of hypothermia. 840 56

Regional protein synthesis of brain was measured by quantitative autoradiography in normo- and hypothermic rats submitted to 30 min of four-vessel occlusion. The tracer, [14C]leucine, was applied by controlled intravenous infusion to achieve constant plasma specific activity, and the admixture by proteolysis of unlabeled amino acids to the brain amino acid precursor pool was corrected by measuring the ratio of the labeled-to-unlabeled leucine distribution space in plasma and brain. In normothermic rats preischemic protein synthesis rate was 16.0 +/- 3.2, 9.2 +/- 3.4, 15.5 +/- 2.8, and 15.5 +/- 3.1 nmol of leucine/g/min (mean +/- SD) in the frontal cortex, striatum, hippocampal CA1 sector, and thalamus, respectively. After 30 min of ischemia at a constant brain temperature of 36 degrees C and a recirculation time of 1 h, protein synthesis was reduced in these regions to 6, 9, 8, and 36%, respectively. With ongoing recirculation, protein synthesis gradually returned to normal within 3 days in all areas except in the stratum pyramidale of the hippocampal CA1 sector where inhibition of neuronal protein synthesis was irreversible. Lowering of brain temperature to 30 degrees C during ischemia did not prevent the early global postischemic depression of protein synthesis, but promoted recovery to or above normal within 6 h in all areas including the stratum pyramidale of the CA1 sector. Improvement of protein synthesis in the CA1 sector was associated with improved neuronal survival, which increased from 1% in the normothermic to 69% in the hypothermic animals. These observations suggest that the protective effect of mild hypothermia on ischemic injury of the hippocampal CA1 sector is mediated by the reversal of the postischemic inhibition of protein synthesis.
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PMID:Protective effect of hypothermia on hippocampal injury after 30 minutes of forebrain ischemia in rats is mediated by postischemic recovery of protein synthesis. 851 67


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