We have previously shown that 5-HT1Breceptors inhibit prejunctionally the rat vasodepressor CGRPergic sensory outflow. Since 5-HT1receptors comprise 5-HT1A, 5-HT1B, 5-HT1Dand 5-HT1Ffunctional subtypes, this study has further investigated the role of 5-HT1A, 5-HT1Dand 5-HT1Freceptor subtypes in the inhibition of the above vasodepressor sensory outflow. Pithed rats were pretreated with i.v. continuous infusions of hexamethonium and methoxamine, followed by 5-HT1receptor agonists. Then electrical spinal stimulation (T9-T12) or i.v. bolus injections of exogenous α-CGRP produced frequency-dependent or dose-dependent vasodepressor responses. The electrically-induced vasodepressor responses remained unchanged during infusions of the 5-HT1Areceptor agonists 8-OH-DPAT and NN-DP-5-CT. In contrast, these responses were inhibited by the agonists sumatriptan (5-HT1A/1B/1D/1F), indorenate (5-HT1A), PNU-142633 (5-HT1D) or LY344864 (5-HT1F), which did not affect the vasodepressor responses to exogenous CGRP (implying a prejunctional sensory-inhibition). When analysing the effects of antagonists: (i) 310 μg/kg (but not 100 μg/kg) GR127935 (5-HT1A/1B/1D/1F) abolished the inhibition to sumatriptan, indorenate, PNU-142633 or LY344864; (ii) 310 μg/kg SB224289 (5-HT1B) or BRL15572 (5-HT1D) failed to block the inhibition to sumatriptan or PNU-142633, whereas SB224289 + BRL15572 partly blocked the inhibition to sumatriptan; and (iii) 10 μg/kg WAY100635 (5-HT1A) failed to block the inhibition to indorenate. These results suggest that 5-HT1F, but not 5-HT1Aor 5-HT1D, receptor subtypes inhibit the vasodepressor sensory CGRPergic outflow although, admittedly, no selective 5-HT1Freceptor agonist is available yet. The pharmacological profile of these receptors resembles that shown in rat dorsal root ganglia by molecular biology techniques.

Additional Metadata
Keywords Blood pressure, CGRP (calcitonin gene-related peptide), LY344864, PNU-142633, Sumatriptan
Persistent URL dx.doi.org/10.1016/j.ejphar.2011.03.035, hdl.handle.net/1765/33425
Citation
González-Hernández, A, Manrique-Maldonado, G, Lozano-Cuenca, J, Muñoz-Islas, E, Centurion, D, Maassen VanDenBrink, A, & Villalón, C.M. (2011). The 5-HT1 receptors inhibiting the rat vasodepressor sensory CGRPergic outflow: Further involvement of 5-HT1F, but not 5-HT 1A or 5-HT1D, subtypes. European Journal of Pharmacology, 659(2-3), 233–243. doi:10.1016/j.ejphar.2011.03.035