QEHA27, 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 (QEHA27) containing the G beta gamma binding motif QXXER, found in adenylyl cyclase 2 and several effector proteins of the G beta gamma-subunit. The patch-clamp technique was utilized to record Ca2+ current from serotonergic dorsal raphe neurons and to introduce the peptide QEHA27 into the cell. We investigated whether it antagonized the inhibitory modulation of Ca2+ current. Compared to the control group, 5-HT was 41% less effective at inhibiting Ca2+ current with 500 microM QEHA27 in the pipette. The QEHA27 peptide did not simply occlude the response to 5-HT because there was no stimulating effect of QEHA27 on the G-protein mediated response. This appears to be the first report of an interference between this peptide 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 -subunit.
Chen
Y
Y
Department of Pharmacology, State University of New York, Brooklyn 11203-2098, USA.
Penington
N J
NJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*
D015220:Calcium Channels; D009479:Neuropeptides; D010446:Peptide Fragments; D012701:Serotonin; D019204:GTP-Binding Proteins; D002118:Calcium