THYROTROPIN-RELEASING-HORMONE RECEPTOR ACTIVATION DOES NOT ELEVATE INTRACELLULAR CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE IN CELLS EXPRESSING HIGH-LEVELS OF RECEPTORS

Activation of TRH receptors (TRH-R) stimulates a signal transduction p athway that leads to the formation of two second messenger molecules, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. It has been sugge sted that TRH may also cause an elevation of another second messenger, cAMP. As adenovirus-mediated gene transfer allows expression of TRH-R to high levels in a number of cell types, we tested again whether TRH -R activation might elevate intracellular cAMP in these more sensitive cell systems. In five cell lines, including three human lines, infect ion with a replication defective adenovirus that encodes the mouse TRH -R complementary DNA (AdCMVmTRHR) induced the expression of 0.2-2 mill ion TRH-R/cell. AdCMVmTRHR-infected cells were activated by a maximall y effective dose of TRH, and the levels of inositol phosphates and cAM P were measured. TRH stimulated the production of inositol phosphates from 5- to 9-fold in all cell types, but did not elevate cAMP in any c ell type. These data confirm that TRH-R activation does not lead to an elevation of intracellular cAMP.