Ghrelin Receptor and Dopamine Receptor Type 2 Co-expression Modifies Each Receptor?s Effects on Voltage Gated Calcium Channel CaV2.2

MUSTAFÁ, EMILIO ROMÁN; CORDISCO GONZALEZ, SANTIAGO; RAINGO, JESICA; RODRÍGUEZ, SILVIA SUSANA

ASN Neuro

ASN American Socierty for Neurochemistry

Año: 2019 vol. 11

1759-0914

Presynaptic CaV2.2 is activated by action potentials, andtheir calcium current induces neurotransmitter release. Inthis context, regulating CaV2.2 is critical, and one of themost important mechanisms for doing so is throughG-protein coupled receptor (GPCR) activity. Two suchGPCRs are the ghrelin receptor (GHSR) and the dopaminereceptor type 2 (D2R). We have previously demonstratedthat GHSR constitutive activity reduces CaV2.2 trafficking tothe plasma membrane and that ghrelin-induced GHSR activity inhibits CaV2.2 currents. On the other hand, dopaminemediated activation of D2R also inhibits CaV2.2 currents. It has been recently shown that D2R and GHSR heterodimerize in hypothalamic neurons. Here, we explore howco-expression of GHSR and D2R modulates the effect thateach GPCR has individually on CaV2.2. We found thatGHSR-D2R co-expression increases the basal inhibition ofCaV2.2 by GHSR constitutive activity, since less GHSR isneeded to reduce CaV2.2 currents when D2R is co-transfected. By contrast, the acute inhibitory effect of ghrelin onCaV2.2 currents is unaffected by GHSR-D2R co-expression.Meanwhile, GHSR-D2R co-expression decreases inhibitionof CaV2.2 by dopamine-evoked D2R activity (increase inEC50), since a higher dopamine concentration is neededto inhibit CaV2.2 currents when GHSR is co-transfected.This last effect depends on GHSR constitutive activity,since it is occluded by pre-incubation with Substance-Panalog 1 mM, a GHSR inverse agonist.