MOLECULAR-CLONING OF A CDNA-ENCODING FOR THE GLP-1 RECEPTOR EXPRESSEDIN RAT LUNG

Recent data revealed the existence, localization and possible function of specific receptors for glucagon-like peptide 1 (7-36) amide (GLP-1 ) in rat lung. This receptor has different biochemical features than t he GLP-1 receptor in endocrine pancreas. Therefore, we aimed to clone the lung receptor cDNA in order to analyze whether biochemical and fun ctional diversity of the GLP-1 receptors in lung and pancreas is based upon genetic differences. A cDNA library from rat lung in a lambda gt 11 vector was screened with a cDNA probe coding for the rat pancreas G LP-1 receptor. Thereby, we found a lung GLP-1 receptor cDNA which show s nearly complete homology to the pancreatic beta-cell receptor cDNA. Only one base exchange occured at base 1 of a codon at position 977 re sulting in a change of valine residue for isoleucine at position 323 o f the amino acid sequence within the fifth transmembrane region. North ern blot hybridization identified transcripts at 2.7, 3.4, and 3.6 Kb. Expression of the recombinant lung GLP-1 receptor cDNA in CHO cells d isplayed a pharmacological profile similar to that seen with cells exp ressing the beta-cell derived cDNA. Therefore, we conclude that tissue -specificity for GLP-1 receptors is based upon posttranslational modif ications of the receptor protein (for example glycosilation) or altern ative splicing of primary transcripts and not on variations within the coding sequence of the receptor gene.