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Icilin induces a hyperthermia in rats that is dependent on nitric oxide production and NMDA receptor activation.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2008 Jan 14; Vol. 578 (2-3), pp. 201-8. Date of Electronic Publication: 2007 Oct 03. - Publication Year :
- 2008
-
Abstract
- Icilin (AG-3-5) is a cold-inducing agent that activates the transient receptor potential channels TRPM8 and TRPA1. Both channels are members of the transient receptor potential (TRP) superfamily of ion channels and are activated by cold. Despite the key role of cold-activated TRPM8 and TRPA1 channels in temperature sensation and other physiological processes, the significance of these channels in thermoregulation in conscious animals is poorly understood. Therefore, in the present study we investigated the effects of icilin on body temperature in rats and tested the hypothesis that cold-activated TRP channel activation by icilin causes a hyperthermia which requires nitric oxide (NO) production and NMDA receptor stimulation. Our experiments revealed that icilin (2.5, 5, 7.5 and 10 mg/kg, i.m.) elicits a dose-related hyperthermia that is rapid in onset and of long duration. Pretreating rats with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (10, 25 and 50 mg/kg, i.p.), a non-selective NO synthase inhibitor, attenuated the hyperthermia associated with icilin (7.5 mg/kg, i.m.). Pretreatment with (-)-6-[phosphonomethyl-1,2,3,4,4a,5,6,7,8,8a-decahydro-isoquinoline-2-carboxylate] (LY 235959) (0.25, 0.5 and 1 mg/kg, i.p.), a selective NMDA receptor antagonist, also attenuated the icilin-evoked hyperthermia. The administration of icilin (5 and 100 microg) into the lateral cerebroventricle of rats did not affect body temperature, thus indicating a peripheral site of action. These results indicate that icilin, a TRPM8/TRPA1 agonist, produces a dose-related hyperthermia in rats which requires both NO production and NMDA receptor activation.
- Subjects :
- Animals
Dose-Response Relationship, Drug
Enzyme Inhibitors pharmacology
Excitatory Amino Acid Antagonists pharmacology
Fever metabolism
Fever physiopathology
Fever prevention & control
Injections, Intramuscular
Injections, Intraperitoneal
Injections, Intraventricular
Isoquinolines pharmacology
Male
NG-Nitroarginine Methyl Ester pharmacology
Nitric Oxide Synthase antagonists & inhibitors
Nitric Oxide Synthase metabolism
Pyrimidinones administration & dosage
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate metabolism
Time Factors
Tremor chemically induced
Behavior, Animal drug effects
Body Temperature drug effects
Fever chemically induced
Nitric Oxide metabolism
Pyrimidinones toxicity
Receptors, N-Methyl-D-Aspartate agonists
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 578
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17976579
- Full Text :
- https://doi.org/10.1016/j.ejphar.2007.09.030