Order of application determines the interaction between phorbol esters and GTP-gamma-S in dorsal raphe neurons: evidence that the effect of 5-HT is modified upstream of the G protein Ca channel interaction

Journal of Neurophysiology
Y Chen, N J Penington

Abstract

Phorbol esters activating protein kinase C (PKC) partially uncouple the inhibitory effect of serotonin (5-HT) from serotonergic neuron Ca2+ current. Presently the site of action of PKC is not known and may be the receptor, G protein, or ion channel. We recorded Ca2+ current from acutely isolated neurons with the use of the patch-clamp technique to study the site of action of PKC. Activation of the G protein with internal guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) occluded the response to 5-HT, but unexpectedly this effect was not reversed by the addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA) despite the voltage-dependent reversal of the effect of GTP-gamma-S by long depolarizing steps to +80 mV. PMA was, however, able to partially reverse 5-HT-induced inhibition of Ca2+ current. The rate of reinhibition of the Ca2+ current (related to the concentration of activated G proteins) by GTP-gamma-S after the addition of PMA at -50 mV was identical to the rate when only GTP-gamma-S was present. By contrast, when cells were exposed first to PMA, and then GTP-gamma-S was perfused into the cell, GTP-gamma-S lost about half of its ability to activate the G protein. The rate of reinhibition of the Ca2+ current by...Continue Reading

References

Jan 1, 1985·Annual Review of Biochemistry·F Eckstein
Sep 1, 1989·Trends in Biochemical Sciences·R Sagi-Eisenberg
Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·Y ZickA M Spiegel
Mar 1, 1995·Trends in Pharmacological Sciences·P Leff
Mar 21, 1996·Nature·S HerlitzeW A Catterall

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