Modulation of GABAArho1 receptors by histamine.

AN BELTRÁN GONZÁLEZ; A OLAVIAGA; P ZUBIRY; DJ CALVO

Congreso; 2nd Federation of Latin American and Caribbean Neuroscience Societies (FALAN) Congress; 2016

Federation of Latin American and Caribbean Neuroscience Societies (FALAN)

Originally known as a peripheral cytokine, histamine is a well-recognized neurotransmitter. In mammals, it modulates arousal, sleep, cognition, learning, appetite and endocrine outputs. Histamine-releasing neurons are located in the tuberomammillary nucleus of the hypothalamus, from where they project throughout the brain. Histamine actions are mediated by metabotropic receptors. In addition, several evidences indicated a possible neumodulatory role of histamine on different ligand gated ion channels. Histamine gates GABAA-beta2/3 receptors and acts as positive allosteric modulator of GABAA-alfa1beta2 and GABAA-alfa1beta2gamma2L and an inverse agonist at 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. 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 antagonized GABAArho1 responses. Inhibition was dose-dependent, reversible, voltage independent and depended on GABA concentration. The mechanism of action is currently under study. This is the first report of a direct action of histamine on tonic GABAA receptors.