title: Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus synaptosomes.
abstract: High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosine A2A receptor (A2AR) stimulation on depolarization-evoked [(3)H]-GABA release. At 3 and 10 nM, the A2AR agonist CGS-21680 enhanced [(3)H]-GABA release induced by high K(+) (20 mM) and the effect of 3 nM CGS-21680 was prevented by the A2AR antagonist ZM-241385 (100 nM). The presence of presynaptic H3Rs was confirmed by the specific binding of N-α-[methyl-(3)H]-histamine to membranes from GP synaptosomes (maximum binding, Bmax, 1327 ± 79 fmol/mg protein; dissociation constant, Kd, 0.74 nM), which was inhibited by the H3R ligands immepip, clobenpropit, and A-331440 (inhibition constants, Ki, 0.28, 8.53, and 316 nM, respectively). Perfusion of synaptosomes with the H3R agonist immepip (100 nM) had no effect on K(+)-evoked [(3)H]-GABA release, but inhibited the stimulatory action of A2AR activation. In turn, the effect of immepip was blocked by the H3R antagonist clobenpropit, which had no significant effect of its own on K(+)-induced [(3)H]-GABA release. These data indicate that H3R activation selectively counteracts the facilitatory action of A2AR stimulation on GABA release from striato-pallidal projections.
authors.affiliation: Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN , Av. Instituto Politécnico Nacional 2508, Zacatenco, 07360 México, D.F., México.
authors.forename: Guadalupe-Elide
authors.initials: GE
authors.lastname: Morales-Figueroa
authors.forename: Ricardo
authors.initials: R
authors.lastname: Márquez-Gómez
authors.forename: Raúl
authors.initials: R
authors.lastname: González-Pantoja
authors.forename: Juan
authors.initials: J
authors.lastname: Escamilla-Sánchez
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Arias-Montaño
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D005917:Globus Pallidus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D017442:Histamine Agonists / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C493218:4'-(3-(3(R)-(dimethylamino)-pyrrolidin-1-yl)-propoxy)-biphenyl-4-carbonitrile; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D001713:Biphenyl Compounds; D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D007093:Imidazoles; D009570:Nitriles; D010627:Phenethylamines; D010880:Piperidines; D011759:Pyrrolidines; D043705:Receptor, Adenosine A2A; D018100:Receptors, Histamine H3; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C085755:4-(1H-imidazol-4-ylmethyl)piperidine; D005680:gamma-Aminobutyric Acid; D013890:Thiourea; D000241:Adenosine; C086108:clobenpropit; D011188:Potassium