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Pharmacology of vanilloids at recombinant and endogenous rat vanilloid receptors
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Pharmacology of vanilloids at recombinant and endogenous rat vanilloid receptors

Author: Vera RalevicJeffrey C JermanStephen J BroughJohn B DavisJulie EgertonAll authors
Edition/Format: Article Article : English
Publication:Biochemical Pharmacology, v65 n1 (2003): 143-151
Other Databases: WorldCatWorldCat
Summary:
This study compared the actions of members of five different chemical classes of vanilloid agonists at the recombinant rat vanilloid VR1 receptor expressed in HEK293 cells, and at endogenous vanilloid receptors on dorsal root ganglion cells and sensory nerves in the rat isolated mesenteric arterial bed. In mesenteric beds, vanilloids elicited dose-dependent vasorelaxation with the rank order of potency:  Read more...
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Document Type: Article
All Authors / Contributors: Vera Ralevic; Jeffrey C Jerman; Stephen J Brough; John B Davis; Julie Egerton; Darren Smart Affiliation: Neurology CEDD, Harlow, UK
ISSN:0006-2952
Language Note: English
Unique Identifier: 4923492612
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Abstract:

This study compared the actions of members of five different chemical classes of vanilloid agonists at the recombinant rat vanilloid VR1 receptor expressed in HEK293 cells, and at endogenous vanilloid receptors on dorsal root ganglion cells and sensory nerves in the rat isolated mesenteric arterial bed. In mesenteric beds, vanilloids elicited dose-dependent vasorelaxation with the rank order of potency: resiniferatoxin⪢capsaicin=olvanil>phorbol 12-phenyl-acetate 13-acetate 20-homovanillate (PPAHV)>isovelleral. Scutigeral was inactive. Responses were abolished by capsaicin pretreatment and inhibited by ruthenium red. In VR1-HEK293 cells and dorsal root ganglion neurones, Ca 2+ responses were induced by resiniferatoxin>capsaicin=olvanil>PPAHV; all four were full agonists. Isovelleral and scutigeral were inactive. The resiniferatoxin-induced Ca 2+ response had a distinct kinetic profile. Olvanil had a Hill coefficient of ∼1 whilst capsaicin, resiniferatoxin and PPAHV had Hill coefficients of ∼2 in VR1-HEK293 cells. The capsaicin-induced Ca 2+ response was inhibited in a concentration-dependent manner by ruthenium red>capsazepine>isovelleral. These data show that resiniferatoxin, capsaicin, olvanil and PPAHV, but not scutigeral and isovelleral, are agonists at recombinant rat VR1 receptors and endogenous vanilloid receptors on dorsal root ganglion neurones and in the rat mesenteric arterial bed. The vanilloids display the same relative potencies (resiniferatoxin>capsaicin=olvanil>PPAHV) in all of the bioassays.

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