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 natural heptapeptide D-Ala-deltorphin II, the most selective agonist for delta-receptors currently available, was used to study the role of brain delta opioid receptors in the control of body temperature. In rats placed in a cold ambient temperature (4 degrees C), intracerebroventricular injections of D-Ala-deltorphin II produced a significant hypothermia. In animals at an ambient temperature of 22 degrees C, only the highest dose employed induced a slight fall in body temperature. At a warm temperature (34 degrees C), D-Ala-deltorphin II induced no significant changes in body temperature. D-Ala-deltorphin II-induced hypothermia, unaffected by naloxone, was significantly reduced by the selective delta receptor antagonist naltrindole. These findings indicate that D-Ala-deltorphin II produces its hypothermic effects at a supraspinal delta receptor, and support the involvement of delta receptors in central control of body temperature.
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PMID:Hypothermic effect of D-Ala-deltorphin II, a selective delta opioid receptor agonist. 131 15

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

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

The neuroprotective effects of hibernation-regulating substances (HRS) such as adenosine (ADO), opioids, histamine and thyrotropin-releasing hormone (TRH) on low-temperature-induced cell death (LTCD) were examined using primary cultured hamster hippocampal neurons. LTCD was induced when cultures were maintained at <22 degrees C for 7 days. ADO (10-100 microM) protected cultured neurons from LTCD in a dose-dependent manner. The neuroprotective effects of ADO were reversed by both 8-cyclopenthyltheophilline (CPT; A(1) receptor antagonist) and 3,7-dimethyl-1-propargylxanthine (DMPX; A(2) receptor antagonist). Morphine (a non-selective opioid receptor agonist) was also effective in attenuating LTCD at an in vitro dose range of 10-100 muM. The neuroprotective effects of morphine were antagonized by naloxone (a non-selective opioid receptor antagonist). In addition, although [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin (DAMGO; mu-opioid receptor agonist), [D-Pen(2,5)]-enkephalin (DPDPE; delta-opioid receptor agonist) and U-69593 (kappa-opioid receptor agonist) were also effective, LTCD of cultured hippocampal neurons was not affected by TRH. Furthermore, histamine produced hypothermia in Syrian hamsters and protected hippocampal neurons in vitro at 100 microM. The neuroprotective effect of histamine was reversed by pyrilamine (H(1) receptor antagonist). Apoptosis was probably involved in LTCD. These results suggest that ADO protected hippocampal neurons in vitro via its agonistic actions on both A(1) and A(2) receptors, whereas morphine probably elicited its neuroprotective effects via agonistic effects on the mu-, delta- and kappa-opioid receptors. In addition, histamine also protected hippocampal neurons via its agonistic action on the H(1) receptor. Thus, HRS-like adenosine-, opioid- and histamine-like hypothermic actions would most likely induce neuroprotective effects against LTCD in vitro.
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PMID:Neuroprotective effects of hibernation-regulating substances against low-temperature-induced cell death in cultured hamster hippocampal neurons. 1685 91

Emergency preservation and resuscitation (EPR) is a new approach for resuscitation of exsanguination cardiac arrest (CA) victims. EPR uses a cold aortic flush to induce deep hypothermic preservation during no-flow to buy time for transport and damage control surgery, followed by resuscitation with cardiopulmonary bypass (CPB). We reported previously that 20-60 min EPR in rats was associated with intact outcome, while 75 min EPR resulted in high mortality and neurological impairment in survivors. The delta opioid agonist DADLE ([D-Ala(2),D-Leu(5)]-enkephalin) was shown previously to be protective against ischemia-reperfusion injury in multiple organs, including brain. We hypothesized that DADLE could augment neurological outcome after EPR in rats. After rapid lethal hemorrhage, EPR was initiated by perfusion with ice-cold crystalloid to induce hypothermia (15 degrees C). After 75 min EPR, resuscitation was attempted with CPB. After randomization, three groups were studied (n=10 per group): DADLE 0mg/kg (D0), 4 mg/kg (D4) or 10mg/kg (D10) added to the flush and during reperfusion. Survival, overall performance category (OPC; 1=normal, 5=death), neurological deficit score (NDS; 0-10% normal, 100%=max deficit), and histological damage score (HDS) were assessed in survivors on day 3. In D0 group, 2/10 rats survived, while in D4 and D10 groups, 4/10 and 5/10 rats survived, respectively (p=NS). Survival time (h) was 26.7+/-28.2 in D0, 36.3+/-31.9 in D4 and 47.1+/-30.3 in D10 groups, respectively (p=0.3). OPC, NDS and HDS were not significantly different between groups. In conclusion, DADLE failed to confer benefit on functional or histological outcome in our model of prolonged rat EPR.
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PMID:Assessment of the delta opioid agonist DADLE in a rat model of lethal hemorrhage treated by emergency preservation and resuscitation. 1974 May 86

Hemorrhagic shock is the leading cause of preventable death after trauma. Hibernation-based treatment approaches have been of increasing interest for various biomedical applications. Owing to apparent similarities in tissue perfusion and metabolic activity between severe blood loss and the hibernating state, hibernation-based approaches have also emerged for the treatment of hemorrhagic shock. Research has shown that hibernators are protected from shock-induced injury and inflammation. Utilizing the adaptive mechanisms that prevent injury in these animals may help alleviate the detrimental effects of hemorrhagic shock in non-hibernating species. This review describes hibernation-based preclinical and clinical approaches for the treatment of severe blood loss. Treatments include the delta opioid receptor agonist D-Ala-Leu-enkephalin (DADLE), the gasotransmitter hydrogen sulfide, combinations of adenosine, lidocaine, and magnesium (ALM) or D-beta-hydroxybutyrate and melatonin (BHB/M), and therapeutic hypothermia. While we focus on hemorrhagic shock, many of the described treatments may be used in other situations of hypoxia or ischemia/reperfusion injury.
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PMID:Hibernation-Based Approaches in the Treatment of Hemorrhagic Shock. 2928 78