IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Presynaptic calcium channels regulation by ghrelin receptor (GHSR1a) activity
Autor/es:
JESICA RAINGO; EDUARDO JAVIER LÓPEZ SOTO; FRANCINA AGOSTI; SILVIA RODRÍGUEZ; MARIO PERELLO
Lugar:
Buenos Aires
Reunión:
Congreso; 5th Special Conference of the International Society for Neurochemistry-?Synapses and dendritic spines in health and disease?; 2012
Resumen:
Understanding the neural mechanisms underlying appetite control has became crucial for public health due to the world obesity pandemic. Currently, many pharmaceutical companies are developing strategies to inhibit central actions of ghrelin, the only peptide hormone known to increase food intake. Thus, a comprehensive understanding of ghrelin neurophysiological effects is necessary to design safe ghrelinbased clinical treatments. Ghrelin acts via the growth hormone secretagogue receptor type 1a (GHSR1a), a G protein coupled receptor that has an unusually high basal activity. In neurons, GHSR1a regulates gene expression, electric activity and neurosecretion. Here we tested whether basal and evoked activity of GHSR1a modifies presynaptic calcium channels activity as a mechanism to control neurotransmitter release. For this, we performed cell-attached patch-clamp recordings in HEK cells expressing GHSR1a and N-type calcium channels (CaV2.2). We found that the amount of GHSR cDNA plasmid used during the transfection inversely correlates with the percentage of transfected cells with detectable CaV2.2 basal current (slope = )88.5 lg)1, r2 = 0.3, n = 22 cells). Of note, the percentage of transfected cells with detectable CaV2.2 basal currents is not affected by a mutated form of GHSR1a that lacks constitutive activity. Ghrelin treatment inhibits CaV2.2 basal current levels in a concentration-dependent manner (16.0 ± 2.1 and 48.8 ± 3.3 % of total CaV2.2 current for ghrelin 100 and 500 nM, respectively). This ghrelin-induced inhibition of CaV2.2 current is partially washable and fully independent of the applied voltage. We thus conclude that basal and evoked GHSR1a activity inhibits presynaptic calcium channels and this effect could account for the physiological effect of ghrelin at presynaptic terminals. We are currently investigating the pathways mediating this effect and the modulation of these pathways by newly synthesized agonist and antagonist of GHSR1a. Supported by PICT2010?1589 and PICT2010?1954.