Presynaptic calcium channels regulation by the ghrelin receptor, growth hormone secretagogue receptor type 1a (GHSR1a) activity

EDUARDO JAVIER LOPEZ SOTO; FRANCINA AGOSTI; MARÍA FLORENCIA ISASA; SILVIA RODRIGUEZ; MARIO PERELLÓ; JESICA RAINGO

Congreso; XXVII congreso de la SAN; 2012

Understanding the neural mechanisms underlying appetite control has became crucial for public health due to the world obesity pandemic. Ghrelin is the only peptide hormone known to increase food intake. Thus, a comprehensive understanding of ghrelin neurophysiological effects is necessary to design safe ghrelin-based clinical treatments. Ghrelin acts via GHSR1a, a G protein coupled receptor that has unusual high basal activity. In neurons, GHSR1a regulates gene expression, electric activity and neurosecretion. Here we tested if 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 HEK293 cells expressing GHSR1a and CaV2.2 channels. We found that the amount of GHSR cDNA plasmid used during the transfection inversely correlates with the CaV2.2 basal current level. Of note, CaV2.2 basal currents level is not affected by the co-expression of a mutated form of GHSR1a that lacks constitutive activity. On the other hand, ghrelin-stimulation inhibits CaV2.2 basal current levels in a concentrationdependent manner. We then conclude that basal and evoked GHSR1a activity inhibits presynaptic calcium channels and this effect could count for thephysiological effect of ghrelin at presynaptic terminals. We are currently investigating the pathways mediating this effect and the effect of newly synthesized agonists and antagonists of GHSR1a.