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Molecular cloning and functional characterization of a rat somatostatin sst 2(b) receptor splice variant
Author(s) -
Schindler Marcus,
Kidd Emma J,
Carruthers Alan M,
Wyatt Mark A,
Jarvie Emma M,
Sellers Lynda A,
Feniuk Wasyl,
Humphrey Patrick P A
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702064
Subject(s) - receptor , agonist , pertussis toxin , melatonin receptor , biology , somatostatin , chinese hamster ovary cell , somatostatin receptor , microbiology and biotechnology , somatostatin receptor 2 , medicine , endocrinology , g protein , biochemistry
1 The mouse somatostatin (SRIF) sst 2 receptor exists in two splice variants, sst 2(a) and sst 2(b) , which differ in their intracellular carboxy‐termini only. The murine sst 2(b) receptor was reported to be less prone to agonist‐induced desensitization as compared with the sst 2(a) receptor. To determine whether a sst 2(b) splice variant with similar functional characteristics exists in the rat, we have isolated a cDNA fragment from rat gastric mucosa encoding a sst 2(b) receptor and expressed the full‐length protein in CHO‐K1 cells for functional characterization. 2 This study provides the first evidence for the occurrence in the rat of the sst 2(b) receptor, which has a 15 amino acid carboxy‐terminus differing in composition to the 38 amino acid C‐terminus of the rat sst 2(a) receptor. 3 In CHO‐K1 cells expressing rat recombinant sst 2(a) or sst 2(b) receptors, SRIF caused concentration‐dependent increases in extracellular acidification rates (EAR) with pEC 50 values of 9.0 and 9.9, respectively. Pre‐treatment with pertussis toxin (Ptx) caused a rightward displacement of the SRIF concentration‐effect curves with pEC 50 values of 8.3 (sst 2(a) ) and 8.4 (sst 2(b) ). 4 SRIF (3 p M –3 n M ) also caused concentration‐dependent inhibition of forskolin‐stimulated cyclic AMP formation in CHO‐sst 2(a) cells (pIC 50 10.5) and CHO‐sst 2(b) cells (pIC 50 10.4). The degree of inhibition was less with higher concentrations of SRIF resulting in bell‐shaped concentration‐effect curves. Following pre‐treatment with Ptx, the inhibitory effect of SRIF was abolished and SRIF caused only increases in cyclic AMP formation. 5 Both the SRIF‐induced increases in EAR and inhibition of cyclic AMP formation were susceptible to agonist‐induced desensitization, but this was less apparent following pre‐treatment with Ptx. 6 This demonstrates that the operational characteristics of the recombinant rat sst 2(a) and sst 2(b) receptors are broadly similar. Both isoforms couple to Ptx‐sensitive as well as ‐insensitive G proteins and are equally prone to agonist‐induced desensitization.British Journal of Pharmacology (1998) 125 , 209–217; doi: 10.1038/sj.bjp.0702064