LOCALIZATION OF SOMATOSTATIN RECEPTOR SUBTYPE MESSENGER-RNA IN THE RAT GASTROINTESTINAL-TRACT AND REGULATION OF SSTR1 GENE-EXPRESSION

Somatostatin and its receptors are widely distributed in the central n ervous system and peripheral tissues including those of the gastrointe stinal tract (GI tract). The expression patterns of the five known SST R genes have been analysed in detail by reverse transcription polymera se chain reaction amplifications and in situ hybridizations using tiss ues dissected from different parts of rat stomach and gut. While SSTR1 mRNA is present at relatively high amounts throughout the gastrointes tinal tract, the levels of SSTR2, 3 and 4 mRNAs vary in different regi ons and SSTR5 mRNA has not been detected. In situ hybridizations revea led the presence of SSTR3 mRNA in enterocytes and in neurons of the my enteric and submucous plexus. These findings are consistent with a rol e of SSTR3 in the observed somatostatin-mediated inhibition of acetylc holine release from myenteric neurons and of secretomotor neuron activ ity in the submucous plexus. Sequence analyses of the SSTR1 gene promo ter revealed the absence of the canonical TATA and CAAT motifs and the presence of a variety of potential binding sites for transcriptional regulators. Among these are binding sites for GCF, AP-2, AP-4, respons e elements for somatostatin (SOM-RE), epidermal growth factor (EGF-RE) and cytocines (GAS and NFIL) as well as for tissue-specific factors s uch as Pit-1 (pituitary) and IDX-1 (pancreatic cells). Mobility shift assays have confirmed that nuclear proteins of pancreatic RIN1046-38 a nd pituitary GH(3) tumour cells bind to oligonucleotides containing th e overlapping Pit-1 and IDX-1 binding sites. Thus, the Pit-1/IDX-1 sit es may be critical for the activation of the SSTR1 gene in these cell- types.