Pharmacological Analysis of P2Y Purinergic Receptors That Modulate the Rat Vasopressor Sympathetic Tone.
6 affiliations
- 1Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas Coapa, Deleg. Tlalpan, Ciudad de Mexico C.P. 14330, Mexico.
- 2Translational Research Centre, Copenhagen University Hospital-Rigshospitalet, Nordstjernevej 42, 2600 Glostrup, Denmark.
- 3Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
- 4Danish Headache Center, Department of Neurology, Copenhagen University Hospital-Rigshospitalet, 2600 Glostrup, Denmark.
- 5Division of Vascular Medicine and Pharmacology, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
- 6Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, C. Lic. Méndez Nieto, s/n, 37007 Salamanca, Spain.
Abstract
Background/Objectives: Adenosine 5'-O-(β-thio)-diphosphate (ADPβS) is a stable analogue of adenosine diphosphate (ADP). In pithed rats, ADPβS produces (i) inhibition of both the cardioaccelerator sympathetic tone (via prejunctional P2Y₁₂/P2Y₁₃ receptors) and the vasodepressor sensory CGRPergic tone (via prejunctional P2Y₁ receptors) and (ii) vasodepressor/vasodilator responses via endothelial P2Y₁ receptors, and vasopressor/vasoconstrictor responses via P2Y₁/P2Y₁₂/P2Y₁₃ receptors. This study pharmacologically investigates whether P2Y₁, P2Y₁₂, and/or P2Y₁₃ receptors modulate the vasopressor sympathetic tone using ADPβS. Methods: A total of 126 male Wistar rats were pithed and classified into two groups to produce vasopressor responses by (i) spinal (T₇-T₉) electrical stimulation of the sympathetic vasopressor tone (0.03-3 Hz; n = 102) and (ii) intravenous (i.v.) boluses of noradrenaline (0.03-3 μg/kg; n = 24). Results: Continuous i.v. infusions of ADPβS (5.6 and 10 μg/kg·min) significantly inhibited the vasopressor responses to sympathetic electrical stimulation, without affecting those induced by exogenous noradrenaline. This sympathoinhibition by ADPβS (5.6 μg/kg·min) remained unchanged after vehicle (1 mL/kg, i.v.) or the antagonists PSB 0739 (P2Y12; 300 μg/kg, i.v.) and MRS 2211 (P2Y13; 1000 and 3000 μg/kg, i.v.). Conversely, it was abolished after MRS 2500 (P2Y1; 300 μg/kg, i.v.) or glibenclamide (KATP channel blocker; 20 mg/kg, i.v.). Conclusions: ADPβS inhibits the vasopressor sympathetic tone via prejunctional P2Y₁ receptors through KATP channel-dependent mechanisms.
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BibTeX
@article{villalon2026pharmacological,
title = {{Pharmacological Analysis of P2Y Purinergic Receptors That Modulate the Rat Vasopressor Sympathetic Tone.}},
author = {Carlos M Villalón and Juan Linares-Bedolla and Belinda Villanueva-Castillo and Alejandro D Miguel-Martínez and Kristian A Haanes and Antoinette MaassenVanDenBrink and Juan F Fernández-González and Eduardo Rivera-Mancilla},
journal = {Pharmaceuticals (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/ph19101594},
url = {https://europepmc.org/article/MED/42943291},
note = {CC BY},
}
RIS
TY - JOUR
TI - Pharmacological Analysis of P2Y Purinergic Receptors That Modulate the Rat Vasopressor Sympathetic Tone.
AU - Carlos M Villalón
AU - Juan Linares-Bedolla
AU - Belinda Villanueva-Castillo
AU - Alejandro D Miguel-Martínez
AU - Kristian A Haanes
AU - Antoinette MaassenVanDenBrink
AU - Juan F Fernández-González
AU - Eduardo Rivera-Mancilla
PY - 2026
DA - 2026/10/08
JO - Pharmaceuticals (Basel, Switzerland)
DO - 10.3390/ph19101594
UR - https://europepmc.org/article/MED/42943291
AB - Background/Objectives: Adenosine 5'-O-(β-thio)-diphosphate (ADPβS) is a stable analogue of adenosine diphosphate (ADP). In pithed rats, ADPβS produces (i) inhibition of both the cardioaccelerator sympathetic tone (via prejunctional P2Y₁₂/P2Y₁₃ receptors) and the vasodepressor sensory CGRPergic tone (via prejunctional P2Y₁ receptors) and (ii) vasodepressor/vasodilator responses via endothelial P2Y₁ receptors, and vasopressor/vasoconstrictor responses via P2Y₁/P2Y₁₂/P2Y₁₃ receptors. This study pharmacologically investigates whether P2Y₁, P2Y₁₂, and/or P2Y₁₃ receptors modulate the vasopressor sympathetic tone using ADPβS. Methods: A total of 126 male Wistar rats were pithed and classified into two groups to produce vasopressor responses by (i) spinal (T₇-T₉) electrical stimulation of the sympathetic vasopressor tone (0.03-3 Hz; n = 102) and (ii) intravenous (i.v.) boluses of noradrenaline (0.03-3 μg/kg; n = 24). Results: Continuous i.v. infusions of ADPβS (5.6 and 10 μg/kg·min) significantly inhibited the vasopressor responses to sympathetic electrical stimulation, without affecting those induced by exogenous noradrenaline. This sympathoinhibition by ADPβS (5.6 μg/kg·min) remained unchanged after vehicle (1 mL/kg, i.v.) or the antagonists PSB 0739 (P2Y12; 300 μg/kg, i.v.) and MRS 2211 (P2Y13; 1000 and 3000 μg/kg, i.v.). Conversely, it was abolished after MRS 2500 (P2Y1; 300 μg/kg, i.v.) or glibenclamide (KATP channel blocker; 20 mg/kg, i.v.). Conclusions: ADPβS inhibits the vasopressor sympathetic tone via prejunctional P2Y₁ receptors through KATP channel-dependent mechanisms.
SN - 1424-8247
ER -