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The Role of Pre‐junctional D 2 ‐like Receptors Mediating Quinpirole‐Induced Inhibition of the Vasodepressor Sensory CGRP ergic Out‐flow in Pithed Rats
Author(s) -
ManriqueMaldonado Guadalupe,
GonzálezHernández Abimael,
AltamiranoEspinoza Alain H.,
MarichalCancino Bruno A.,
RuizSalinas Inna,
Villalón Carlos M.
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12122
Subject(s) - quinpirole , receptor , medicine , sensory system , endocrinology , neuroscience , chemistry , pharmacology , biology , dopamine receptor
Calcitonin gene‐related peptide ( CGRP ) released from perivascular sensory nerves plays a role in the regulation of vascular tone. Indeed, electrical stimulation of the perivascular sensory out‐flow in pithed rats produces vasodepressor responses, which are mainly mediated by CGRP release. This study investigated the potential role of dopamine D 1 ‐like and D 2 ‐like receptors in the inhibition of these vasodepressor responses. For this purpose, male Wistar pithed rats (pre‐treated i.v. with 25 mg/kg gallamine and 2 mg/kg min. hexamethonium) received i.v. continuous infusions of methoxamine (20 μg/kg min.) followed by physiological saline (0.02 ml/min.), the D 1 ‐like receptor agonist SKF ‐38393 (0.1–1 μg/kg min.) or the D 2 ‐like receptor agonist quinpirole (0.03–10 μg/kg min.). Under these conditions, electrical stimulation (0.56–5.6 Hz; 50 V and 2 ms) of the thoracic spinal cord (T 9 –T 12 ) resulted in frequency‐dependent vasodepressor responses which were (i) unchanged during the infusions of saline or SKF ‐38393 and (ii) inhibited during the infusions of quinpirole (except at 0.03 μg/kg min.). Moreover, the inhibition induced by 0.1 μg/kg min. quinpirole (which failed to inhibit the vasodepressor responses elicited by i.v. bolus injections of exogenous α‐ CGRP ; 0.1–1 μg/kg) was (i) unaltered after i.v. treatment with 1 ml/kg of either saline or 5% ascorbic acid and (ii) abolished after 300 μg/kg (i.v.) of the D 2 ‐like receptor antagonists haloperidol or raclopride. These doses of antagonists (enough to completely block D 2 ‐like receptors) essentially failed to modify per se the electrically induced vasodepressor responses. In conclusion, our results suggest that quinpirole‐induced inhibition of the vasodepressor sensory CGRP ergic out‐flow is mainly mediated by pre‐junctional D 2 ‐like receptors.