Lipopolysaccharide fever is initiated via a capsaicin-sensitive mechanism independent of the subtype-1 vanilloid receptor - PubMed (original) (raw)

Comparative Study

. 2004 Dec;143(8):1023-32.

doi: 10.1038/sj.bjp.0705977. Epub 2004 Oct 18.

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Comparative Study

Lipopolysaccharide fever is initiated via a capsaicin-sensitive mechanism independent of the subtype-1 vanilloid receptor

M Devrim Dogan et al. Br J Pharmacol. 2004 Dec.

Abstract

As pretreatment with intraperitoneal capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP), an agonist of the vanilloid receptor known as VR1 or transient receptor potential channel-vanilloid receptor subtype 1 (TRPV-1), has been shown to block the first phase of lipopolysaccharide (LPS) fever in rats, this phase is thought to depend on the TRPV-1-bearing sensory nerve fibers originating in the abdominal cavity. However, our recent studies suggest that CAP blocks the first phase via a non-neural mechanism. In the present work, we studied whether this mechanism involves the TRPV-1. Adult Long-Evans rats implanted with chronic jugular catheters were used. Pretreatment with CAP (5 mg kg(-1), i.p.) 10 days before administration of LPS (10 microg kg(-1), i.v.) resulted in the loss of the entire first phase and a part of the second phase of LPS fever. Pretreatment with the ultrapotent TRPV-1 agonist resiniferatoxin (RTX; 2, 20, or 200 microg kg(-1), i.p.) 10 days before administration of LPS had no effect on the first and second phases of LPS fever, but it exaggerated the third phase at the highest dose. The latter effect was presumably due to the known ability of high doses of TRPV-1 agonists to cause a loss of warm sensitivity, thus leading to uncontrolled, hyperpyretic responses. Pretreatment with the selective competitive TRPV-1 antagonist capsazepine (N-[2-(4-chlorophenyl)ethyl]-1,3,4,5-tetrahydro-7,8-dihydroxy-2H-2-benzazepine-2-carbothioamidem, CPZ; 40 mg kg(-1), i.p.) 90 min before administration of LPS (10 microg kg(-1), i.v.) or CAP (1 mg kg(-1), i.p.) did not affect LPS fever, but blocked the immediate hypothermic response to acute administration of CAP. It is concluded that LPS fever is initiated via a non-neural mechanism, which is CAP-sensitive but RTX- and CPZ-insensitive. The action of CAP on this mechanism is likely TRPV-1-independent. It is speculated that this mechanism may be the production of prostaglandin E(2) by macrophages in LPS-processing organs.

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Figures

Figure 1

Figure 1

Effects of pretreatment with CAP (5 mg kg−1, i.p.) or vehicle on the following responses: the body temperature response to LPS (10 _μ_g kg−1, i.v.) or saline (a); the relative difference in the amount of food consumed by food-deprived rats during a 30-min period after administration of CCK-8 sulfate (6 _μ_g kg−1, i.p.) or saline (b); and the number of eye wipes during a 30-s period after intraocular administration of a drop of 1% NH4OH (c).

Figure 2

Figure 2

Effects of pretreatment with RTX (2 _μ_g kg−1, i.p.) or vehicle on the following responses: the body temperature response to LPS (10 _μ_g kg−1, i.v.) or saline (a); the relative difference in the amount of food consumed by food-deprived rats during a 30-min period after administration of CCK-8 sulfate (6 _μ_g kg−1, i.p.) or saline (b); and the number of eye wipes during a 30-s period after intraocular administration of a drop of 1% NH4OH (c).

Figure 3

Figure 3

Effects of pretreatment with RTX (20 _μ_g kg−1, i.p.) or vehicle on the following responses: the body temperature response to LPS (10 _μ_g kg−1, i.v.) or saline (a); the relative difference in the amount of food consumed by food-deprived rats during a 30-min period after administration of CCK-8 sulfate (6 _μ_g kg−1, i.p.) or saline (b); and the number of eye wipes during a 30-s period after intraocular administration of a drop of 1% NH4OH (c).

Figure 4

Figure 4

Effects of pretreatment with RTX (200 _μ_g kg−1, i.p.) or vehicle on the following responses: the body temperature response to LPS (10 _μ_g kg−1, i.v.) or saline (a); the relative difference in the amount of food consumed by food-deprived rats during a 30-min period after administration of CCK-8 sulfate (6 _μ_g kg−1, i.p.) or saline (b); and the number of eye wipes during a 30-s period after intraocular administration of a drop of 1% NH4OH (c).

Figure 5

Figure 5

Effects of pretreatment with CPZ (40 mg kg−1, i.p.) or vehicle on the following responses: the body temperature response to LPS (10 _μ_g kg−1, i.v.) or saline (a) and CAP (1 mg kg−1, i.p.)-induced hypothermia (b). CPZ was administered 90 min before LPS or CAP.

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References

    1. AVELINO A., CRUZ F. Peptide immunoreactivity and ultrastructure of rat urinary bladder nerve fibers after topical desensitization by capsaicin or resiniferatoxin. Auton. Neurosci. 2000;86:37–46. - PubMed
    1. BEVAN S., HOTHI S., HUGHES G., JAMES I.F., RANG H.P., SHAH K., WALPOLE C.S.J., YEATS J.C. Capsazepine: a competitive antagonist of the sensory neuron excitant capsaicin. Br. J. Pharmacol. 1992;107:544–552. - PMC - PubMed
    1. BÍRÓ T., MAURER M., MODARRES S., LEWIN N.E., BRODIE C., ÁCS G., ÁCS P., PAUS R., BLUMBERG P.M. Characterization of functional vanilloid receptors expressed by mast cells. Blood. 1998;91:1332–1340. - PubMed
    1. CATERINA M.J., LEFFLER A., MALMBERG A.B., MARTIN W.J., TRAFTON J., PETERSEN-ZEITZ K.R., KOLTZENBURG M., BASBAUM A.I., JULIUS D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288:306–313. - PubMed
    1. CATERINA M.J., ROSEN T.A., TOMINAGA M., BRAKE A.J., JULIUS D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature. 1999;398:436–441. - PubMed

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