title: Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats.
abstract: Metabotropic P2Y receptors subfamily consists of eight functional mammalian receptors. Specifically, P2Y1, P2Y6 and P2Y11 receptors have been described in the sensory nervous system, but their participation, at peripheral level, in behavioral pain models is scarcely understood. This study assessed the role of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain. Ipsilateral, but not contralateral peripheral pre-treatment with the endogenous P2Y1 (ADP, 100-1000nmol/paw), P2Y6 (UDP, 180-300nmol/paw) and P2Y11 (ATP, 100-1000nmol/paw), or selective P2Y1 (MRS2365, 0.1-10nmol/paw), P2Y6 (PSB0474, 0.1-0.10pmol/paw) and P2Y11 (NF546, 0.3-3nmol/paw) receptor agonists increased 0.5% formalin-induced flinching behavior. Concordantly, peripheral pre-treatment with the selective P2Y1 (MRS2500, 0.01-10pmol/paw), P2Y6 (MRS2578, 3-30nmol/paw) and P2Y11 (NF340, 1-10nmol/paw) receptor antagonists significantly decreased 1% formalin-induced flinching behavior. Furthermore, the pronociceptive effect of ADP (100nmol/paw) or MRS2365 (10nmol/paw), UDP (300nmol/paw) or PSB0474 (10pmol/paw) and ATP (1000nmol/paw) or NF546 (3nmol/paw) was blocked by the selective P2Y1 (MRS2500, 0.01nmol/paw), P2Y6 (MRS2578, 3nmol/paw), and P2Y11 (NF340, 1nmol/paw) receptor antagonists, respectively. Western blot analysis confirmed the presence of P2Y1 (66kDa), P2Y6 (36kDa) and P2Y11 (75kDa) receptors in dorsal root ganglia (DRG) and sciatic nerve. Results suggest that peripheral activation of P2Y1, P2Y6 and P2Y11 receptors plays a pronociceptive role in formalin-induced pain.
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico. Electronic address: costa_tutecq@hotmail.com.
authors.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico. Electronic address: coolmanx10@hotmail.com.
authors.forename: Luis
authors.initials: L
authors.lastname: Mendoza-Garcés
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico. Electronic address: ilovedanae@yahoo.com.mx.
authors.forename: Jorge Baruch
authors.initials: JB
authors.lastname: Pineda-Farias
authors.affiliation: Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Secretaría de Salud, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, 14080 México, D.F., Mexico. Electronic address: solanovero17@yahoo.com.mx.
authors.forename: Verónica
authors.initials: V
authors.lastname: Solano-Olivares
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico. Electronic address: jrsilverio61@yahoo.com.mx.
authors.forename: Juan
authors.initials: J
authors.lastname: Rodríguez-Silverio
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico; Unidad de Investigación en Farmacología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Secretaría de Salud, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, 14080 México, D.F., Mexico. Electronic address: fjfloresmurrieta@yahoo.com.mx.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Flores-Murrieta
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico. Electronic address: vinicio_granadossoto@hotmail.com.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico. Electronic address: hector.isaac@gmail.com.
authors.forename: Héctor Isaac
authors.initials: HI
authors.lastname: Rocha-González
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology; D017879:Isothiocyanates / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D059226:Nociceptive Pain / Q000139:chemically induced / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D058910:Purinergic P2 Receptor Agonists / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1 / Q000502:physiology*; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014530:Uridine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
chemical_list: C000597001:3-(2-oxo-2-phenylethyl)uridine-5'-diphosphate; D017879:Isothiocyanates; C541384:N,N''-1,4-butanediylbis(N'-(3-isothiocyanatophenyl))thiourea; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; C099845:purinoceptor P2Y6; D005557:Formaldehyde; D014530:Uridine Diphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D013890:Thiourea
keywords: Formalin test; Inflammatory pain; P2Y(1); P2Y(11); P2Y(6); Purinergic receptors