Open AccessThe role of purinergic P2Y12 and P2Y13 receptors in ADPβS-induced inhibition of the cardioaccelerator sympathetic drive in pithed rats
Author(s) -
Belinda VillanuevaCastillo,
Eduardo RiveraMancilla,
Kristian Agmund Haanes,
Antoinette MaassenVanDenBrink,
Carlos M. Villalón
Publication year - 2020
Publication title -
purinergic signalling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 59
eISSN - 1573-9546
pISSN - 1573-9538
DOI - 10.1007/s11302-020-09689-z
Subject(s) - purinergic receptor , medicine , endocrinology , p2 receptor , receptor , receptor antagonist , antagonist , p2y receptor , chemistry , adenosine , stimulation , ppads , purinergic signalling , neurotransmitter , p2y12 , pharmacology , biology , adenosine receptor , agonist , platelet , platelet aggregation
ATP is a cotransmitter released with other neurotransmitters from sympathetic nerves, where it stimulates purinergic receptors. Purinergic adenosine P 1 receptors (coupled to G i/o proteins) produce sympatho-inhibition in several autonomic effectors by prejunctional inhibition of neurotransmitter release. Similarly, signalling through P2Y 12 and P2Y 13 receptors coupled to G i/o proteins is initiated by the ATP breakdown product ADP. Hence, this study has pharmacologically investigated a possible role of ADP-induced inhibition of the cardioaccelerator sympathetic drive in pithed rats, using a stable ADP analogue (ADPβS) and selective antagonists for the purinergic P2Y 1 , P2Y 12 and P2Y 13 receptors. Accordingly, male Wistar rats were pithed and: (i) pretreated i.v. with gallamine (25 mg/kg) and desipramine (50 μg/kg) for preganglionic spinal (C 7 -T 1 ) stimulation of the cardioaccelerator sympathetic drive (n = 78); or (ii) prepared for receiving i.v. injections of exogenous noradrenaline (n = 12). The i.v. continuous infusions of ADPβS (10 and 30 μg/kg/min) dose-dependently inhibited the tachycardic responses to electrical sympathetic stimulation, but not those to exogenous noradrenaline. The cardiac sympatho-inhibition produced by 30 μg/kg/min ADPβS was (after i.v. administration of compounds) (i) unchanged by 1-ml/kg bidistilled water or 300-μg/kg MRS 2500 (P2Y 1 receptor antagonist), (ii) abolished by 300-μg/kg PSB 0739 (P2Y 12 receptor antagonist) and (iii) partially blocked by 3000-μg/kg MRS 2211 (P2Y 13 receptor antagonist). Our results suggest that ADPβS induces a cardiac sympatho-inhibition that mainly involves the P2Y 12 receptor subtype and, probably to a lesser extent, the P2Y 13 receptor subtype. These receptors may represent therapeutic targets for treating cardiovascular pathologies, including stroke and myocardial infarctions.