The long isoform of the rat thyrotropin-releasing hormone receptor down-regulates Gq proteins.

摘要: Abstract A cDNA encoding the long isoform of rat thyrotropin releasing hormone (TRH) receptor was expressed stably in HEK-293 cells. Polymerase chain reaction analysis confirmed expression mRNA only and not short isoform. Activation this with TRH caused a large stimulation production inositol phosphates but did produce either activation basal or inhibition forskolin-amplified adenylyl cyclase activity. Sustained exposure these transfected cells to resulted substantial reduction cellular levels Gq alpha-like immunoreactivity from some 12 5 pmol/mg membrane protein without significant alterations alpha subunits Gs, Gi1, Gi2, Gi3, Go. Equivalent experiments GH3 also indicated marked down-regulation alpha/G11 alpha. Dose-response curves that 20 nM produced half-maximal Gq-like loss within 3-4 h. Separation cell membranes SDS-polyacrylamide gel electrophoresis conditions able resolve individual members family G-proteins demonstrated presence two related G-proteins. Both were observed be down-regulated parallel by TRH. The similarity dose-response time-courses for indicates does functionally select between transducer proteins. In both G11 alpha, which are at similar levels, equivalently treatment