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  • Title: Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtype.
    Author: Yamada Y, Kagimoto S, Kubota A, Yasuda K, Masuda K, Someya Y, Ihara Y, Li Q, Imura H, Seino S.
    Journal: Biochem Biophys Res Commun; 1993 Sep 15; 195(2):844-52. PubMed ID: 8373420.
    Abstract:
    Somatostatin exerts diverse effects in various tissues upon binding its specific membrane receptors. Recently, we have cloned three different somatostatin receptor subtypes. Here we report the sequence and functional expression of a fourth and a fifth human somatostatin receptor subtype, termed hSSTR4 and hSSTR5, respectively. The hSSTR4 encodes a protein of 388 amino acids and the hSSTR5 is a protein of 364 amino acids. There is 42-60% identity among the amino acid sequences of the five human somatostatin receptor subtypes identified to date. RNA blotting studies reveal that the hSSTR4 is expressed as a single transcript of 4.8 kb in MIA PaCa-2 cells, a cell line derived from human pancreatic cancer while the hSSTR5 is undetectable in the tissues examined. The hSSTR4 and hSSTR5 transiently expressed in COS1 cells exhibit specific binding to somatostatin-14 with IC50 values of 1.6 and 0.16 nM, respectively. We also have characterized the binding affinity of various somatostatin analogues to the hSSTR4 and hSSTR5. The rank of the potency of the analogues are: somatostatin-14 = somatostatin-28 >> RC-160 >> SMS201-995 for the hSSTR4 and somatostatin-28 > somatostatin-14 >> RC-160 > SMS201-995 for the hSSTR5. These results suggest that diverse actions of somatostatin are mediated by at least five somatostatin receptor subtypes with potentially different function.
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