Figure 4

Role of MAP kinase in the inhibitory effect of IGF-1 on the 5-HT response in Xenopus oocytes. Plotted are peak Cl- currents in response to 5-HT after the indicated treatments. (A) The MEK kinase inhibitor, PD 098059, but not the protein kinase C inhibitor (PKC I), blocks the inhibitory effect of IGF-1 on the 5-HT response. The data are presented as the mean ± S.E.M. of 6 oocytes (*, P < 0.05). (B) Activated MAP kinase mimics the IGF-1 inhibitory effect on the 5-HT response. The data are presented as the mean ± S.E.M. of 8-12 oocytes (*, P < 0.05). (C) Mutation of the putative MAP kinase site on the 5-HT2C receptor abolishes the insulin effect. In oocytes expressing the wild-type 5-HT2C receptor (left two bars), insulin treatment resulted in a significant reduction of the peak Cl- current in response to 5-HT. In cells expressing the MAP kinase site mutation S159A (right two bars), insulin had no effect on the 5-HT-activated Cl- current. The data are presented as the mean ± S.E.M. of 6 oocytes (*, P < 0.05).