TRH regulates Kv1.5 gene expression through a G alpha q-mediated PLC-independent pathway

Thyrotropin-releasing hormone (TRH) decreases transcription of the Kv1.5 K channel gene in GH(3) pituitary cells. Here, we examine whether TRH utiliz es Gq activated phospholipase C, Gs or Gi to produce this response. We repo rt that expression of constitutively active G alpha q mimicked and occluded the TRH effect. In contrast, expression of activated G alpha(s) or G alpha (i2) had no effect on Kv1.5 mRNA expression. Furthermore, pertussis and cho lera toxins failed to block the TRH-induced decrease in channel mRNA. Surpr isingly, despite the role of Gq, the phospholipase C inhibitor U73122 did n ot alter down-regulation of channel mRNA by TRH, although it abolished the TRH-induced increase in intracellular [Ca2+] and up-regulation of c-fos mRN A. Furthermore, depletion of an intracellular Ca2+ pool or inhibition of pr otein kinase C did not block the TRH-induced decrease in Kv1.5 mRNA. These results indicate that TRH-induced down-regulation of Kv1.5 gene expression is mediated by G alpha q proteins, but does not require PLC activation. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.