Functional Characterization of the Prejunctional Receptors Mediating the Inhibition by Ergotamine of the Rat Perivascular Sensory Peptidergic Drive
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.
|Persistent URL||dx.doi.org/10.1021/acschemneuro.8b00611, hdl.handle.net/1765/118880|
|Journal||Acs Chemical Neuroscience|
González-Hernández, A, Marichal-Cancino, B.A, Lozano-Cuenca, J, Maassen van den Brink, A, & Villalon, C.M. (2019). Functional Characterization of the Prejunctional Receptors Mediating the Inhibition by Ergotamine of the Rat Perivascular Sensory Peptidergic Drive. Acs Chemical Neuroscience, 10(7), 3173–3182. doi:10.1021/acschemneuro.8b00611