REGULATION OF THE HUMAN SEROTONIN TRANSPORTER BY INTERLEUKIN-1-BETA

The serotonin transporter expressed in brain, platelets, and placenta is a primary target for antidepressants, cocaine, and amphetamines. He re we report that interleukin-1 beta is a potent regulator of the expr ession of this transporter. The activity of the serotonin transporter in human JAR choriocarcinoma cells is stimulated by this cytokine and the stimulation is accompanied by an increase in the steady state leve ls of the transporter mRNAs and in the transporter density. The increa se in mRNA levels is effectively blocked by actinomycin D. The stimula tory effect of interleukin-1 beta is not associated with any change in the cellular levels of cAMP, indicating involvement of a cAMP-indepen dent pathway. Even though cholera toxin, which is known to increase cA MP levels, also upregulates the serotonin transporter in JAR cells, th e effects of interleukin-1 beta and cholera toxin on the transporter a ctivity are additive. This constitutes the first report on the identif ication of a physiologically occurring hormone/cytokine which upregula tes the expression of the human serotonin transporter gene. (C) 1995 A cademic Press, Inc.