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 pathway that leads to the formation of two second messenger molecules, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. It has been suggested 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, infection with a replication defective adenovirus that encodes the mouse TRH-R complementary DNA (AdCMVmTRHR) induced the expression of 0.2-2 million TRH-R/cell. AdCMVmTRHR-infected cells were activated by a maximally effective dose of TRH, and the levels of inositol phosphates and cAMP 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 cell type. These data confirm that TRH-R activation does not lead to an elevation of intracellular cAMP.
Heinflink
M
M
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Nussenzveig
D R
DR
Friedman
A M
AM
Gershengorn
M C
MC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D008113:Liver Neoplasms; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D007295:Inositol Phosphates; D018025:Receptors, Thyrotropin-Releasing Hormone; D005576:Colforsin; D013973:Thyrotropin-Releasing Hormone; D000242:Cyclic AMP