CLONING AND CHARACTERIZATION OF A 4TH HUMAN SOMATOSTATIN RECEPTOR

We have isolated a gene coding for a fourth human somatostatin (somato tropin release-inhibiting factor) receptor. This additional somatostat in receptor (hSSTR4) is specifically expressed in human fetal and adul t brain and lung tissue. The deduced amino acid sequence of the recept or displays both sequence and structural homology to three cloned soma tostatin receptors as well as to other members of the family of GTP-bi nding-protein-coupled seven-helix transmembrane-spanning receptors. Ph armacological characterization of the expressed receptor reveals speci fic, high-affinity binding of somatostatin 14 and somatostatin 28. Sur prisingly, several well-characterized synthetic somatostatin analogs f ail to exhibit high-affinity binding to hSSTR4, indicating the existen ce of pharmacologically different receptor subtypes. Our data suggest that the diverse biological effects exerted by somatostatin are mediat ed by a family of receptors with discrete patterns of expression and d ifferent pharmacological properties.