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A human somatostatin receptor (SSTR3), located on chromosome 22, displays preferential affinity for somatostatin‐14 like peptides
Author(s) -
Corness Jacquie D.,
Demchyshyn Lidia L.,
Seeman Philip,
Van Tol Hubert H.M.,
Srikant Coimbatore B.,
Kent Gillian,
Patel Yogesh C.,
Niznik Hyman B.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80124-d
Subject(s) - somatostatin receptor , biology , somatostatin receptor 1 , somatostatin receptor 3 , somatostatin , somatostatin receptor 2 , receptor , biochemistry , microbiology and biotechnology , peptide sequence , endocrinology , medicine , gene
We report here on the cloning of a human intronless gene encoding a member of the G‐protein linked somatostatin (SST) receptor subfamily, termed SSTR3. Based on the deduced amino acid sequence, this gene encodes a 418 amino acid protein displaying sequence similarity, particularly within putative transmembrane domains, with the recently cloned human SSTR1 (62%), SSTR2 (64%) and SSTR4 (58%) receptors. Membranes prepared from COS‐7 cells transiently expressing the human SSTR3 gene bound [ 125 I]Leu 8 , d ‐Trp 22 ,‐Tyr 22 SST‐28 in a saturable manner with high affinity (~200 pM) and with rank order of potency ( d ‐Trp 8 SST‐14 > SST‐14 > SMS‐201‐995 > SST‐28) indicative of a somatostatin‐14 selective receptor. The pharmacological profile of the expressed human SSTR3 receptor is similar but not identical to that reported for the rat homolog [(1992) J. Biol. Chem. 267,20422] where the peptide selectivity is SST‐28 ≧ SST‐14 XXX SMS‐201‐995. Northern blot analysis reveals the presence of an SSTR3 mRNA species of ~5 kb in various regions of the monkey brain, including the frontal cortex, cerebellum, medulla, amygdala, with little or no SSTR3 mRNA detectable in brain regions such as the striatum, hippocampus, and olfactory tubercle. The SSTR3 receptor gene maps to human chromosome 22. The existence of at least four distinct human genes encoding somatostatin‐14 selective receptors with diverse pharmacological specificities may help to account for some of the multiple biological actions of somatostatin under normal and pathological conditions.