TY - JOUR
T1 - Activation of 5-HT1B receptors inhibits the vasodepressor sensory CGRPergic outflow in pithed rats
AU - González-Hernández, Abimael
AU - Muñoz-Islas, Enriqueta
AU - Lozano-Cuenca, Jair
AU - Ramírez-Rosas, Martha B.
AU - Sánchez-López, Araceli
AU - Centurión, David
AU - Juan, Eduardo Ramírez San
AU - Villalón, Carlos M.
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - (Pithed rat)
KW - 5-HT receptor
KW - CP-93,129
KW - SB224289
KW - α-CGRP
UR - http://www.scopus.com/inward/record.url?scp=77953286233&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2010.03.053
DO - 10.1016/j.ejphar.2010.03.053
M3 - Artículo
SN - 0014-2999
VL - 637
SP - 131
EP - 137
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -