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Functional Characterization of the Prejunctional Receptors Mediating the Inhibition by Ergotamine of the Rat Perivascular Sensory Peptidergic Drive.

Abstract：

:Calcitonin gene-related peptide (α-CGRP) released from perivascular sensory nerves induces decreases in diastolic blood pressure (DBP). Experimentally, this can be shown by spinal thoracic (T9-T12) electrical stimulation of these afferent fibers. Because ergotamine inhibits these neurogenic vascular responses and displays affinity for monoaminergic receptors that inhibit neurotransmitter release, we investigated whether this ergotamine-induced inhibition results from activation of serotonin 5-HT1B/1D, dopamine D2-like, and α2-adrenergic receptors. Wistar rats were pithed and, under autonomic ganglion blockade, received intravenous infusions of methoxamine followed by ergotamine (0.1-3.1 μg kg-1 min-1). Thoracic T9-T12 electrical stimulation or an intravenous bolus of α-CGRP resulted in decreases in DBP. Ergotamine inhibited the electrically induced, but not α-CGRP-induced, responses. The vasodilator sensory inhibition by 3.1 μg of ergotamine kg-1 min-1 was resistant to simultaneous blockade of 5-HT1B/1D, D2-like, and α2-adrenergic receptors upon addition of antagonists GR127935, haloperidol, and rauwolscine. Moreover, the inhibition by 0.31 μg of ergotamine kg-1 min-1 was unaltered by GR127935 and haloperidol, partly blocked by GR127935 and rauwolscine or rauwolscine and haloperidol, and abolished by GR127935, haloperidol, and rauwolscine. These findings imply that prejunctional 5-HT1B/1D, D2-like, and α2-adrenergic receptors mediate the sensory inhibition induced by 0.31 μg of ergotamine kg-1 min-1, whereas larger doses may involve other receptors. Thus, ergotamine's ability to inhibit the perivascular sensory peptidergic drive may result in facilitation of its systemic vasoconstrictor properties.

journal_name

ACS Chem Neurosci

journal_title

ACS chemical neuroscience

authors

González-Hernández A,Marichal-Cancino BA,Lozano-Cuenca J,MaassenVanDenBrink A,Villalón CM

doi

10.1021/acschemneuro.8b00611

subject

Has Abstract

pub_date

2019-07-17 00:00:00

pages

3173-3182

issue

issn

1948-7193

journal_volume

pub_type

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Functional Characterization of the Prejunctional Receptors Mediating the Inhibition by Ergotamine of the Rat Perivascular Sensory Peptidergic Drive.