INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Inhibition of GABAA-rho1 receptor function by histamine
Autor/es:
ZUBIRY, P; BELTRÁN GONZALEZ A; CALVO, DJ; OLAVIAGA, A
Lugar:
Mar del Plata
Reunión:
Congreso; Reunión anual 2016 SAIC SAI SAFE; 2016
Institución organizadora:
SAIC SAI SAFE
Resumen:
ID 853Inhibition of GABAA-rho1 receptor function by histamineBeltrán González AN, Zubiry P, Olaviaga A and Calvo DJ.Laboratorio de Neurobiología Celular y Molecular. INGEBI-CONICET.Histamine, a local mediator of the immune response, can also act as neurotransmitter and neuromodulator. Histamine-releasing neurons, located in the tuberomammillary nucleus of the hypothalamus, project all over the brain and are involved in the control of arousal, sleep, cognition, learning, appetite and endocrine output. Histamine actions are commonly mediated by metabotropic receptors, but several evidences indicated that histamine can also modulate the function of different ligand gated ion channels. For example, histamine gates homomeric GABAA-beta2 and GABAA-beta3 receptors with a higher efficacy than GABA and is a positive allosteric modulator of heteromeric GABAA-alfa1beta2 and GABAA-alfa1beta2gamma2L receptors and an inverse agonist of strychnine sensitive glycine receptors.In retinal bipolar neurons, ambient concentrations of GABA elicit tonic currents mediated by GABAA-rho1 receptors. The retina receives histaminergic input from the brain via retinopetal axons. The role of histamine in the retina is still far from being entirely understood. In the present study we analyzed the effect of histamine on responses mediated by GABAA-rho1 receptors. Homomeric GABAA-rho1 receptors were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents were recorded by two-electrode voltage-clamp. Histamine inhibited GABAA-rho1 receptor responses. Inhibition was dose-dependent, reversible, voltage independent and depended on GABA concentration. Pre-incubation or repeated applications of histamine gave similar results. This is the first report of a direct modulatory action of histamine on tonic GABAA receptors. The underlying mechanism of action is currently under study.