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)

Various peptide hormones appear to exert behavioral and pharmacologic effects apart from their classical endocrine actions. Thytrotopin-releasing hormone (TRH), for example, antagonizes the sedation and hypothermia produced by barbiturate and other depressant drugs and de Wied has shown that ACTH 4-10, TRH, LHRH and certain related substances show some activity in inhibition of extinction of a pole-jumping avoidance response in the rat. These data provided the impetus for screening ACTH 4-10, LHRH, and related peptides for analeptic activity. ACTH 4-10 and ACTH 4-7 were inactive in antagonizing pentobarbital whether administered peripherally or centrally. ACTH 4-7 amide and 4-Met(O2), 8-D-Lys,9-Phe-ACTH 4-9 were active regardless of route of administration LHRH and two tripeptide fragments (pGlu-His-Trp-NH, and pGlu-His-Phe-NH2) showed analeptic activity only after intracisternal administration. Thus, some peptide fragments related to ACTH 4-10 and LHRH were shown to share to some degree the analeptic properties previously demonstrated for TRH.
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PMID:Comparison of the analeptic potency of TRH, ACTH 4-10, LHRH, and related peptides. 18 24

Bilateral injection of naloxone (3.0-30.0 nmol) into the substantia nigra of morphine-dependent rats produced a withdrawal syndrome consisting of wet-dog shakes, teeth chattering, irritability to touch, diarrhea and hypothermia. Intense wet-dog shakes and grooming were observed after intranigral injection of the mu selective antagonist D-Phe-Cys-Try-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, 3.0-30.0 nmol) in morphine-dependent animals. Body temperature after 30.0 nmol CTOP was significantly increased. A significant positive correlation between body temperature and wet-dog shakes was observed in morphine-dependent animals that received CTOP. Intranigral injection of beta-funaltrexamine (beta-FNA, 10.0 nmol), an irreversible mu antagonist, produced no signs of withdrawal in morphine-dependent animals. However, intranigral injection of beta-FNA (1.0-3.0 nmol) suppressed the antinociceptive effect of the mu-selective agonist, D-Ala2,N-Me-Phe4,Gly5-ol-enkephalin (DAGO, 1.0 nmol). The withdrawal syndrome produced by CTOP (10.0 nmol) was not suppressed by the administration of U50,488H (10.0 nmol), a kappa agonist, suggesting that the absence of an effect of beta-FNA was not due to its kappa agonist activity. Neither the delta-selective antagonist, naltrindole (NTI, 10.0 nmol) nor the kappa-selective antagonist, nor-binaltorphimine (nor-BNI, 10.0 nmol) produced withdrawal. Only wet-dog shakes were observed when CTOP, NTI and nor-BNI (5 nmol each) were administered together into the nigra. These studies suggest an involvement of mu receptors in the nigra in the wet-dog shakes and thermoregulatory dysfunction that occur during withdrawal of morphine. However, the subtypes of opioid receptors in the nigra, that mediate the other signs of morphine withdrawal remain obscure.
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PMID:Further studies of the role of opioid receptors in the nigra in the morphine withdrawal syndrome. 135 41

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

The ability of the selective cyclic mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), to inhibit the acute and chronic effects of morphine in vivo was studied in mice. Intracerebroventricular (i.c.v.) administration of CTOP antagonized the analgesic effect of morphine in a dose-dependent manner, as measured by the heat-irradiant (tail-flick) method. CTOP was more effective than naloxone in inhibiting analgesia on a molar basis. CTOP also antagonized the acute morphine-induced hypermotility. CTOP caused withdrawal hypothermia and a loss of body weight in morphine-dependent animals. After the development of morphine-induced chronic dependence, CTOP administered i.c.v. caused a dose-dependent loss of body weight and hypothermia, and was about 10-400 times more potent than naloxone. CTOP administered alone to drugnaive mice did not cause antinociception, changes in body weight or body temperature.
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PMID:Central effects of the potent and highly selective mu opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) in mice. 290 58

The catabolic response that commonly occurs after major operation is characterized by net skeletal muscle proteolysis and accelerated nitrogen excretion. This response was absent in patients undergoing cardiac surgical procedures associated with the combination of cardiopulmonary bypass, narcotic anesthesia, neuromuscular blockade, and hypothermia. Forearm nitrogen release was 422 +/- 492 nmol/100 ml X min on the first postoperative day, approximately 25% of preoperative values (1677 +/- 411, p less than 0.05). Nitrogen excretion and the degree of negative nitrogen balance were comparable to levels observed in nonstressed, fasting subjects. The potential role of hypothermia, high-dose fentanyl anesthesia, and neuromuscular blockade in modifying the catabolic response to laparotomy and retroperitoneal dissection was further evaluated in animal studies. Six hours after operation, amino acid nitrogen release from the hindquarter was 84% less than control values (p less than 0.05). Nitrogen excretion and urea production were also reduced compared to normothermic controls. It is concluded that the combination of hypothermia, narcotic anesthesia, and neuromuscular blockade attenuates the catabolic response to injury and thus may be useful in the care of critically ill surgical patients.
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PMID:Hypothermic anesthesia attenuates postoperative proteolysis. 376 77

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


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