Potentiation of capsaicin-induced neurogenic inflammation by 5-HT7 receptors in the rat hind paw: Involvement of calcitonin gen-related peptide
Autor: | Deni M. Galindo-González, Jessica G. Solis-Anguiano, José A. Terrón, Marcello Leopoldo, Frida Altamirano-Reyna, Luis D. Arreola-Peralta, Enza Lacivita |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Agonist Male Physiology medicine.drug_class TRPV1 Stimulation Pharmacology Calcitonin gene-related peptide Substance P Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Phenols Calcitonin Gene-Related Peptide Receptor Antagonists medicine Animals Humans Neurons Afferent Receptor Neurogenic inflammation Sulfonamides Chemistry Foot Receptor antagonist Rats 030104 developmental biology Receptors Serotonin Capsaicin Neurogenic Inflammation LP-44 030217 neurology & neurosurgery Receptors Calcitonin Gene-Related Peptide |
Zdroj: | Peptides. 105 |
ISSN: | 1873-5169 |
Popis: | A decrease in the activation threshold of primary sensory neurons to transient receptor potential V1 (TRPV1) stimulation by serotonin 5-HT7 receptors has been reported but no confirmation if this might translate into facilitation of neurogenic inflammation has been provided. We analysed the modulation of capsaicin (CAP)-induced neurogenic inflammation in the rat hind paw by the selective 5-HT7 receptor agonist, LP-44, and the involvement of calcitonin gen-related peptide (CGRP) in this effect. Animals received intra-plantar injections (30 μL) of vehicle, CAP (0.05%, 0.1% and 0.2%), LP-44 (7.5 and 15 nmol) and the combination of LP–44 + CAP; then, the time course of the inflammatory responses was measured. The effect of the 5-HT7 receptor antagonist, SB-269970 (3 mg/kg, s.c.), on responses produced by LP-44 alone and combined with CAP was tested. As expected, CAP produced concentration- and time-dependent inflammatory responses in the hind paw. Interestingly, LP-44 by itself also produced inflammation in a concentration- and time-dependent manner, and magnified CAP-induced responses. Systemic pre-treatment with SB-269970 significantly blunted LP-44 (15 nmol)-induced inflammation as well as magnified inflammatory responses produced by the combination of LP-44 (7.5 and 15 nmol) + CAP (0.1%) thus confirming the involvement of 5-HT7 receptors. Finally, the non-peptide CGRP receptor antagonist, BIBN4096 (3 mg/kg, s.c.), strongly inhibited the potentiated inflammatory responses induced by LP-44 (7.5 and 15 nmol) + CAP (0.1%) thus substantiating their neurogenic nature. Thus, sensitization of CAP-sensitive primary sensory neurons by 5-HT7 receptors may result in facilitation of neurogenic inflammation involving CGRP in the rat hind paw. |
Databáze: | OpenAIRE |
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