Activation of 5-HT1B receptors inhibits the vasodepressor sensory CGRPergic outflow in pithed rats

Abimael González-Hernández, Enriqueta Muñoz-Islas, Jair Lozano-Cuenca, Martha B. Ramírez-Rosas, Araceli Sánchez-López, David Centurión, Eduardo Ramírez San Juan, Carlos M. Villalón

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15 Scopus citations

Abstract

The importance of calcitonin gene-related peptide (CGRP) in the regulation of vascular tone has been widely documented. Indeed, stimulation of the perivascular sensory outflow in pithed rats results in vasodepressor responses, which are mediated by CGRP release. These vasodepressor responses are inhibited by clonidine via prejunctional α2A/2C-adrenoceptors, but no study has yet reported the role of prejunctional 5-hydroxytryptamine (5-HT) receptors in this experimental model. Since activation of prejunctional 5-HT1 receptors results in inhibition of neurotransmitter release, this study sets out to investigate as an initial approach the role of 5-HT1B receptors in the inhibition of the vasodepressor sensory outflow in pithed rats. Male Wistar pithed rats were pretreated with hexamethonium (2mg/kg.min) followed by i.v. continuous infusions of methoxamine (20μg/kg.min), and then by saline (0.02ml/min) or CP-93,129 (a rodent 5-HT1B receptor agonist; 0.1, 1 and 10μg/kg.min). Under these conditions, electrical stimulation (0.56-5.6Hz; 50V and 2ms) of the spinal cord (T9-T12) resulted in frequency-dependent decreases in diastolic blood pressure. The infusions of CP-93,129, as compared to those of saline, inhibited the vasodepressor responses induced by electrical stimulation without affecting those to i.v. bolus injections of exogenous α-CGRP (0.1, 0.18, 0.31, 0.56 and 1 μg/kg). This inhibition by CP-93,129 was abolished by the antagonists GR127935 (5-HT1B/1D) or SB224289 (5-HT1B), but not by BRL15572 (5-HT1D). The above results suggest that CP-93,129-induced inhibition of the vasodepressor (perivascular) sensory outflow in pithed rats is mainly mediated by activation of prejunctional 5-HT1B receptors.

Original languageEnglish
Pages (from-to)131-137
Number of pages7
JournalEuropean Journal of Pharmacology
Volume637
Issue number1-3
DOIs
StatePublished - Jul 2010

Keywords

  • (Pithed rat)
  • 5-HT receptor
  • CP-93,129
  • SB224289
  • α-CGRP

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