Identification of a functional 3',5'-cyclic adenosine monophosphate response element within the second promoter of...

Important physiological actions of somatostatin are mediated by the somatostatin receptor type 2. Its transcription is regulated by three tissue specific, alternative promoters. It is known that the mRNA of the somatostatin receptor type 2 gene is induced by cAMP, but little is known about the mechanisms underlying this regulation. We have identified and characterized a cAMP responsive element located at nucleotide -162 on the second promoter of the gene consisting of the classical palindromic octameric sequence 5'-TGACGTCA-3'. Using transient expression of reporter gene deletion constructs in NGC108-15 cells the necessity of the intact element for forskolin-induced reporter gene activity was demonstrated. The first and the third promoter are not responsive to forskolin, nor did any promoter respond to the phorbol ester PMA. Electrophoretic mobility shift assays in combination with competition experiments suggest the interaction of the promoter element with the cAMP responsive element binding protein.