QEHA(27), A PEPTIDE THAT BINDS TO G-PROTEIN BETA-GAMMA-SUBUNITS, REDUCES THE INHIBITORY EFFECT OF 5-HT ON THE CA2+ CURRENT OF RAT DORSAL RAPHE NEURONS

We studied a 27 amino acid peptide (QEHA(27)) containing the G beta ga mma binding motif QXXER, found in adenylyl cyclase 2 and several effec tor proteins of the G beta gamma-subunit. The patch-clamp technique wa s utilized to record Ca2+ current from serotonergic dorsal raphe neuro ns and to introduce the peptide QEHA(27), into the cell. We investigat ed whether it antagonized the inhibitory modulation of Ca2+ current. C ompared to the control group, 5-HT was 41% less effective at inhibitin g Ca2+ current with 500 mu M QEHA(27) in the pipette. The QEHA(27) pep tide did not simply occlude the response to 5-HT because there was no stimulating effect of QEHA(27) on the G-protein mediated response. Thi s appears to be the first report of an interference between this pepti de and the modulation of Ca2+ currents; it suggests that at least part of the action of the G-protein may be mediated by a beta gamma-subuni t. (C) 1997 Elsevier Science Ireland Ltd.