Increases in vanilloid TRPV1 receptor protein and CGRP content during endotoxemia in rats.
The aim of the present study was to determine whether the transient receptor potential vanilloid (TRPV1) receptor protein as well as the calcitonin gene-related peptide (CGRP) content could be enhanced after the i.p. administration of 5 mg/kg lipopolysaccharide (LPS) to Sprague-Dawley rats. In tongue tissue, used as a representative model of TRPV1 receptors expression, there was a significant increase in the abundance of TRPV1 receptor protein 6 h after LPS administration. In mesenteric arteries, the density of the CGRP-positive nerves as well as the release of CGRP induced by 10 microM anandamide was also significantly increased 6 h after LPS administration. The relaxant responses induced by anandamide in mesenteric beds isolated from either untreated or LPS-treated rats were abolished after a 2 h exposure to 10 microM capsaicin. Moreover, anandamide-induced relaxations of untreated mesenteries were potentiated by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 0.1 microM), but not by its inactive analogue 4alpha-phorbol (0.1 microM). The potentiation of anandamide effects caused by the PKC activator was accompanied by a significant increase in the overflow of CGRP induced by anandamide in the untreated rats. It is proposed that the overexpression of the TRPV1 receptors and the increased content of CGRP could contribute to the enhancement of anandamide effects during the endotoxemic shock. An eventual phosphorylation event linked to the overflow of CGRP could also participate in the enhanced relaxation caused by anandamide in endotoxemia.
Orliac
María Luz
ML
Instituto de Investigaciones Farmacológicas (ININFA-CONICET), Junín 956, 5 piso C1113AAD Buenos Aires, Argentina.
Peroni
Roxana N
RN
Abramoff
Tamara
T
Neuman
Isabel
I
Podesta
Ernesto J
EJ
Adler-Graschinsky
Edda
E
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis*; D063388:Endocannabinoids; D019446:Endotoxemia / Q000209:etiology / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D008643:Mesentery / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014059:Tongue / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D001095:Arachidonic Acids; D063388:Endocannabinoids; D008070:Lipopolysaccharides; D010704:Phorbols; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014662:Vasoconstrictor Agents; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide; D013755:Tetradecanoylphorbol Acetate; C078814:anandamide; D009638:Norepinephrine; C033085:phorbol