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)

To the authors' knowledge, the effect of i.t. administered calcium on thermoregulation in mice has not been investigated. Calcium administration (i.t.) induced hypothermia in mice. It was found that calcitonin gene-related peptide (CGRP) (i.t.) also produced hypothermia. Because opioids have well documented thermoregulatory effects, the authors evaluated whether the hypothermia induced by calcium and CGRP was the result of the release of opioids. Calcium induced hypothermia at different ambient temperatures (4 degrees C, 22 degrees C and 30 degrees C) in intact mice. Similarly treated spinalized mice maintained body temperature. Using laser Doppler flowmetry, there was a significant increase in blood flow in the tails of calcium-injected mice vs. those of vehicle-injected mice. Both naloxone and naltrindole failed to block the hypothermic effects of calcium (i.t.). Nor-binaltorphimine (i.t.) significantly blocked calcium (i.t.)-induced changes in body temperature. CGRP (i.t.) produced hypothermia for 15 hr postinjection, with the maximum decrease at 3 hr. CGRP induced hypothermia in intact and sham-lesioned mice but not in spinalized mice. CGRP (i.c.v.) also produced hypothermia (onset, 15-min postinjection) followed by the peak effect at 1 hr with recovery to baseline temperature by 2 hr. Subthreshold doses of calcium and CGRP given in combination produced greater than additive hypothermia. The hypothermic effects of CGRP were reversed by naloxone, naltrindole and nor-binaltorphimine. CGRP produced significant hypothermia in both morphine-tolerant and nontolerant mice. Chronic administration of CGRP in nontolerant and morphine-tolerant mice did not alter hypothermia after pretreatment with CGRP (i.t.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of endogenous opioids as mediators of the hypothermic effects of intrathecally administered calcium and calcitonin gene-related peptide in mice. 837 Nov 46

Lipopolysaccharide (LPS), an endotoxin, produces pain behavior, inflammation, and changes in immune function. Many of these effects are secondary to the production of cytokines. In the present study, we investigated the effect of LPS on the releasing function of afferent terminals as measured by calcitonin gene-related peptide (CGRP) release in ex vivo perfused rat trachea, and examined the possible role of the cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as intermediaries in this effect. Systemic injection of LPS (0.75 mg/kg, i.p.) in adult rats induced an increase in body temperature followed by hypothermia, indicating ongoing infection. We observed that capsaicin-induced (0.1 microM) tracheal CGRP release was significantly enhanced in the LPS-treated animals after 5 hr. This enhancement of the peptide release by LPS was blocked by IL-1beta tripeptide antagonist Lys-D-Pro-Thr (10 microM) and mimicked by IL-1beta and TNF-alpha (10-100 pg/ml), suggesting that the potentiating effect of LPS on CGRP release is mediated by generation of IL-1beta and TNF-alpha. IL-1beta-induced augmentation of CGRP release was blocked by Lys-D-Pro-Thr. Additionally, the cyclooxygenase inhibitor ketorolac (10 microM) significantly attenuated the facilitatory effects of LPS and IL-1b, indicating involvement of prostanoids. These findings suggest that endotoxin treatment generated cytokines such as IL-1b and TNF-alpha that regulated the peripheral releasing function of primary sensory afferents by sensitizing the terminals and facilitating peptide release. This effect is prostanoid dependent.
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PMID:Involvement of cytokines in lipopolysaccharide-induced facilitation of CGRP release from capsaicin-sensitive nerves in the trachea: studies with interleukin-1beta and tumor necrosis factor-alpha. 876 61

Moderate hypothermia significantly diminishes consequences of spinal and cerebral anoxia. One component of this neuroprotection has been hypothesized to be suppression of excitotoxic transmitter release. Whether this suppression is attributable to reduced hypoxic injury that induces release or an alteration of the release process itself is unclear. We sought to characterize the temperature sensitivity (Q10) of basal and evoked calcitonin gene-related peptide (CGRP) and amino acid release from dorsal horn slices of rat spinal cord over a range of temperatures from 40 to 8 degrees C. At 40 degrees C, potassium (60 mM) and capsaicin (10 microM) evoked a 21- and 32-fold increase in basal CGRP concentrations, respectively. Capsaicin had no effect on glutamate release, but potassium evoked a 2.7-fold increase. Release evoked by either potassium or capsaicin was reduced in a biphasic fashion with declining temperature. Over the range of 40 to 34 degrees C, the Q10 values for evoked release for CGRP were 11.3 (potassium) and 39.7 (capsaicin) and for glutamate, 5. 5 (potassium). Over the range of 34 to 8 degrees C, Q10 values were near unity for all evoked release (0.8 and 1.3 for CGRP and 1.2 for glutamate). Although serine, glycine, glutamine, taurine, and citrulline showed no evoked release, basal levels were reduced at temperatures below 34 degrees C. The pronounced temperature dependency of evoked transmitter release between 40 and 34 degrees C is consistent with the profound cerebral protection observed with mild hypothermia in which metabolic activity is only slightly depressed.
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PMID:Temperature dependency of basal and evoked release of amino acids and calcitonin gene-related peptide from rat dorsal spinal cord. 915 57

The delayed preconditioning of the heart by monophosphoryl lipid A is mediated by endogenous nitric oxide (NO), and the cardioprotection afforded by nitroglycerin is related to stimulation of calcitonin gene-related peptide (CGRP) release. The objective of this study was to explore whether improvement of preservation with cardioplegia by monophosphoryl lipid A is mediated by CGRP. In addition, we examined the effect of monophosphoryl lipid A on the tumor necrosis factor-alpha (TNF-alpha) content of myocardial tissues. The isolated rat heart was perfused in the Langendorff mode. Heart rate, coronary flow, left-ventricular pressure, and its first derivatives (+/-dp/dt(max)) were recorded, and plasma levels of NO and CGRP, the release of creatine kinase in coronary effluent and the content of TNF-alpha in myocardial tissues were measured. Hypothermic ischemia for 4 h caused a decline in cardiac function, and an increase in the release of creatine kinase and in the content of TNF-alpha. Pretreatment with monophosphoryl lipid A (500 microg/kg, i.p.) for 24 h improved the recovery of cardiac function and reduced the release of creatine kinase concomitantly with a decrease in the content of cardiac TNF-alpha. Monophosphoryl lipid A markedly increased plasma concentrations of CGRP and NO. After pretreatment with L-nitroarginine methyl ester (L-NAME), the cardioprotection and the increased release of NO and CGRP induced by monophosphoryl lipid A were abolished. Capsaicin also abolished the cardioprotection and the increased release of CGRP induced by monophosphoryl lipid A, but did not affect the content of NO. The results suggest that monophosphoryl lipid A-induced preconditioning enhances preservation with cardioplegia and that the protective effects of monophosphoryl lipid A are related to stimulation of CGRP release.
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PMID:Monophosphoryl lipid A-induced delayed preconditioning is mediated by calcitonin gene-related peptide. 1140 36

Previous investigations have shown that calcitonin gene-related peptide (CGRP) protects against myocardial ischemia-reperfusion injury and that rutaecarpine activates vanilloid receptors to evoke CGRP release. In the present study, we examined whether rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts, and whether the protective effects of rutaecarpine are related to stimulation of endogenous CGRP release via activating vanilloid receptors. The isolated guinea-pig heart was arrested using St. Thomas Hospital solution, and then reperfused with normothermic Krebs-Henseleit solution for 30 min after a 4-h hypothermic ischemic period. Hypothermic ischemia caused a decline in cardiac function (left ventricular pressure, +/-dp/dt(max), heart rate and coronary flow) and an increased release of creatine kinase during reperfusion. Rutaecarpine at the concentration of 1.0 microM significantly improved the recovery of cardiac function and reduced the release of creatine kinase during reperfusion after hypothermic ischemia. Rutaecarpine at the concentration of 3.0 microM significantly reduced the release of creatine kinase and increased the coronary flow, but only caused a slight improvement of left ventricular pressure, +/-dp/dt(max), heart rate during reperfusion. The cardioprotective effects of rutaecarpine were abolished by capsazepine, a competitive vanilloid receptor antagonist, or by CGRP (8-37), a selective CGRP receptor antagonist. Rutaecarpine at the concentration of 1.0 or 3.0 microM significantly increased the release of CGRP, which was also abolished by capsazepine. These results suggest that rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts and that the protective effects of rutaecarpine are due to stimulation of endogenous CGRP release via activating vanilloid receptors.
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PMID:The cardioprotection of rutaecarpine is mediated by endogenous calcitonin related-gene peptide through activation of vanilloid receptors in guinea-pig hearts. 1222 92

Arachidonylethanolamide (anandamide, AEA) is believed to be the endogenous ligand of the cannabinoid CB(1) and CB(2) receptors. CB(1) receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioral effects of anandamide are antinociception, catalepsy, hypothermia, and depression of motor activity, similar to Delta(9)-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study, we looked at the possible role of the CB(1) receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, calcitonin gene-related peptide (CGRP) by 30%, capsaicin by 45%, and nitric oxide by 40%. CGRP(8-37) was also able to attenuate nitric oxide (NO)-induced dilation by 50%. The anandamide inhibition was reversed by the CB(1) receptor antagonist AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both presynaptically, to prevent CGRP release from trigeminal sensory fibers, and postsynaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB(1) receptors seem to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a noncannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system.
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PMID:Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception. 1471 91

The TRPV1 capsaicin receptor is an integrator molecule on primary afferent neurones participating in inflammatory and nociceptive processes. The present paper characterizes the effects of JYL1421 (SC0030), a TRPV1 receptor antagonist, on capsaicin-evoked responses both in vitro and in vivo in the rat. JYL1421 concentration-dependently (0.1-2 microM) inhibited capsaicin-evoked substance P, calcitonin gene-related peptide and somatostatin release from isolated tracheae, while only 2 microM resulted in a significant inhibition of electrically induced neuropeptide release. Capsazepine (0.1-2 microM), as a reference compound, similarly diminished both capsaicin-evoked and electrically evoked peptide release. JYL1421 concentration-dependently decreased capsaicin-induced Ca(2+) accumulation in cultured trigeminal ganglion cells, while capsazepine was much less effective. In vivo 2 mg/kg i.p. JYL1421, but not capsazepine, inhibited capsaicin-induced hypothermia, eye wiping movements and reflex hypotension (a component of the pulmonary chemoreflex or Bezold-Jarisch reflex). Based on these data JYL1421 is a more selective and in most models also a more potent TRPV1 receptor antagonist than capsazepine, therefore it may promote the assessment of the (patho)physiological roles of the TRPV1 receptor.
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PMID:Pharmacological characterization of the TRPV1 receptor antagonist JYL1421 (SC0030) in vitro and in vivo in the rat. 1597 75

Glycyrrhetinic Acid and its salts and esters and Glycyrrhizic Acid and its salts and esters are cosmetic ingredients that function as flavoring agents or skin-conditioning agents - miscellaneous or both. These chemicals may be isolated from licorice plants. Glycyrrhetinc Acid is described as at least 98% pure, with 0.6% 24-OH-Glycyrrhetinic Acid, not more than 20 mu g/g of heavy metals and not more than 2 mu g/g of arsenic. Ammonium Glycyrrhizate has been found to be at least 98% pure and Dipotassium Glycyrrhizate has been found to be at least 95% pure. Glycyrrhetinic Acid is used in cosmetics at concentrations of up to 2%; Stearyl Glycyrrhetinate, up to 1%; Glycyrrhizic Acid, up to 0.1%; Ammonium Glycyrrhizate, up to 5%; Dipotassium Glycyrrhizate, up to 1%; and Potassium Glycyrretinate, up to 1%. Although Glycyrrhizic Acid is poorly absorbed by the intestinal tract, it may be hydrolyzed to Glycyrrhetinic Acid by a beta -glucuronidase produced by intestinal bacteria. Glycyrrhetinic Acid and Glycyrrhizic Acid bind to rat and human albumin, but do not absorb well into tissues. Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites are mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for transepidermal permeation through pig skin. Glycyrrhizic Acid increased the dermal penetration of diclofenac sodium in rat skin. Dipotassium Glycyrrhizate increased the intestinal absorption of calcitonin in rats. In humans, Glycyrrhetinic Acid potentiated the effects of hydrocortisone in the skin. Moderate chronic or high acute exposure to Glycyrrhizic Acid, Ammonium Glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis; possibly through inhibition of 11beta -hydroxysteroid dehydrogenase-2 (11beta -OHSD2) in the kidney. Glycyrrhetinic Acid and its derivatives block gap junction intracellular communication in a dose-dependent manner in animal and human cells, including epithelial cells, fibroblasts, osteoblasts, hepatocytes, and astrocytes; at high concentrations, it is cytotoxic. Glycyrrhetinic Acid and Glycyrrhizic Acid protect liver tissue from carbon tetrachloride. Glycyrrhizic Acid has been used to treat chronic hepatitis, inhibiting the penetration of the hepatitis A virus into hepatocytes. Glycyrrhetinic Acid and Glycyrrhizic Acid have anti-inflammatory effects in rats and mice. The acute intraperitoneal LD(50) for Glycyrrhetinic Acid in mice was 308 mg/kg and the oral LD(50) was > 610 mg/kg. The oral LD(50) in rats was reported to be 610 mg/kg. Higher LD(50) values were generally reported for salts. Little short-term, subchronic, or chronic toxicity was seen in rats given ammonium, dipotassium, or disodium salts of Glycyrrhizic Acid. Glycyrrhetinic Acid was not irritating to shaved rabbit skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents in mice. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion in mice. Glycyrrhizic Acid delayed mortality in mice injected with Erlich ascites tumor cells, but did not reduce the mortality rate. Ammonium Glycyrrhizate was not genotoxic in in vivo and in vitro cytogenetics assays, the dominant lethal assay, an Ames assay, and heritable translocation tests, except for possible increase in dominant lethal mutations in rats given 2000 mg/kg day(-1) in their diet. Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day(-1) for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity in rats, mice, golden hamsters, or Dutch-belted rabbits, except for a dose-dependent increase (at 238.8 and 679.9 mg/kg day(-1)) in sternebral variants in a study using rats. Sedation, hypnosis, hypothermia, and respiratory depression were seen in mice given 1250 mg/kg Glycyrrhetinic Acid intraperitoneally. Rats fed a powdered diet containing up to 4% Ammonium Glycyrrhizate had no treatment related effects in motor function tests, but active avoidance was facilitated at 4%, unaffected at 3%, and depressed at 2%. In a study of 39 healthy volunteers, a no effect level of 2 mg/kg/day was determined for Glycyrrhizic Acid given orally for 8 weeks. Clinical tests in seven normal individuals given oral Ammonium Glycyrrhizate at 6 g/day for 3 days revealed reduced renal and thermal sweat excretion of Na+ and K+, but carbohydrate and protein metabolism were not affected. Glycyrrhetinic Acid at concentrations up to 6% was not a skin irritant or a sensitizer in clinical tests. Neither Glycyrrhizic Acid, Ammonium Glycyrrhizate, nor Dipotassium Glycyrrhizate at 5% were phototoxic agents or photosensitizers. Birth weight and maternal blood pressure were unrelated to the level of consumption of Glycyrrhizic Acid in 1049 Finnish women with infants, but babies whose mother consumed > 500 mg/wk were more likely to be born before 38 weeks. The Cosmetic Ingredient Review (CIR) Expert Panel noted that the ingredients in this safety assessment are not plant extracts, powders, or juices, but rather are specific chemical species that may be isolated from the licorice plant. Because these chemicals may be isolated from plant sources, however, steps should be taken to assure that pesticide and toxic metal residues are below acceptable levels. The Panel advised the industry that total polychlorobiphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and that toxic metal levels must not contain more than 3 mg/kg of arsenic (as As), not more than 0.002% heavy metals, and not more than 1 mg/kg of lead (as Pb). Although the Panel noted that Glycyrrhizic Acid is cytotoxic at high doses and ingestion can have physiological effects, there is little acute, short-term, subchronic, or chronic toxicity and it is expected that these ingredients would be poorly absorbed through the skin. These ingredients are not considered to be irritants, sensitizers, phototoxic agents, or photosensitizers at the current maximum concentration of use. Accordingly, the CIR Expert Panel concluded that these ingredients are safe in the current practices of use and concentration. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe.
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PMID:Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate. 1761 33