A human somatostatin receptor (SSTR3), located on chromosome 22, displays preferential affinity for somatostatin‐14 like peptides

FEBS Letters

Patel, Yogesh C.³  Srikant, Coimbatore B.³  Van Tol, Hubert H.M.¹  Niznik, Hyman B.¹  Seeman, Philip¹  Demchyshyn, Lidia L.²  Kent, Gillian³  Corness, Jacquie D.² 

[1] Departments of Psychiatry, University of Toronto, Toronto, Ont., Canada;Departments of Pharmacology, University of Toronto, Toronto, Ont., Canada;Fraser Laboratories, Departments of Medicine, Neurology and Neurosurgery, McGill University, Royal Victoria Hospital and Montreal Neurological Institute, Montreal, Canada

关键词: Polymerase chain reaction;    Neuropeptide;    SST-14;    SST-28;    SST;    somatostatin;    SSTR;    somatostatin receptor;    G;    guanine nucleotide;   

DOI  :  10.1016/0014-5793(93)80124-D

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 [¹²⁵I]Leu⁸,d-Trp²²,-Tyr²² SST-28 in a saturable manner with high affinity (~200 pM) and with rank order of potency (d-Trp⁸ 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.

【 授权许可】

Unknown