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 ability of various oximes to antagonize the sarin-induced hypothermia and reactivate phosphorylated acetylcholinesterase was used as an indicator of the central activity of oximes. HI-6, but neither toxogonin nor PAM Cl, antagonized sarin-induced hypothermia and reactivated brain acetylcholinesterase, in particular hypothalamic acetylcholinesterase. The sarin-induced hypothermia appears to be a muscarinic cholinergic action since atropine was also an effective antagonist of sarin-induced hypothermia. Neither HI-6 nor toxogonin antagonized oxotremorine-induced hypothermia, indicating that these oximes do not possess central cholinolytic activity. The results demonstrated that HI-6 penetrated the blood-brain barrier in a sufficient concentration to produce a biochemical and physiological action against sarin poisoning.
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PMID:Central activity of acetylcholinesterase oxime reactivators. 173 41

Oleamide (cis-9-octadecenamide) is a member of an emerging class of lipid-signaling molecules, the primary fatty acid amides. A growing body of evidence indicates that oleamide mediates fundamental neurochemical processes including sleep, thermoregulation, and nociception. Nevertheless, the mechanism for oleamide biosynthesis remains unknown. The leading hypothesis holds that oleamide is synthesized from oleoylglycine via the actions of the peptide amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The present study investigated this hypothesis using pharmacologic treatments, physiologic assessments, and measurements of serum oleamide levels using a newly developed enzyme-linked immunosorbant assay (ELISA). Oleamide and oleoylglycine both induced profound hypothermia and decreased locomotion, over equivalent dose ranges and time courses, whereas, closely related compounds, stearamide and oleic acid, were essentially without effect. While the biologic actions of oleamide and oleoylglycine were equivalent, the two compounds differed dramatically with respect to their effects on serum levels of oleamide. Oleamide administration (80mg/kg) elevated blood-borne oleamide by eight-fold, whereas, the same dose of oleoylglycine had no effect on circulating oleamide levels. In addition, pretreatment with the established PAM inhibitor, disulfiram, produced modest reductions in the hypothermic responses to both oleoylglycine and oleamide, suggesting that the effects of disulfiram were not mediated through inhibition of PAM and a resulting decrease in the formation of oleamide from oleoylglycine. Collectively, these findings raise the possibilities that: (1) oleoylglycine possesses biologic activity that is independent of its conversion to oleamide and (2) the increased availability of oleoylglycine as a potential substrate does not drive the biosynthesis of oleamide.
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PMID:In vivo evidence that N-oleoylglycine acts independently of its conversion to oleamide. 1708 22