Molecular cloning and functional characterization of a rat somatostatin sst(2(b)) receptor splice variant

Schindler, M., Kidd, Emma Jane ORCID: https://orcid.org/0000-0001-5507-1170, Carruther, A. M., Wyatt, M. A., Jarvie, E. M., Sellers, L. A., Feniuk, W. and Humphrey, P. P. A. 1998. Molecular cloning and functional characterization of a rat somatostatin sst(2(b)) receptor splice variant. British Journal of Pharmacology 125 (1) , pp. 209-217. 10.1038/sj.bjp.0702064

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Abstract

1The mouse somatostatin (SRIF) sst2 receptor exists in two splice variants, sst2(a) and sst2(b), which differ in their intracellular carboxy-termini only. The murine sst2(b) receptor was reported to be less prone to agonist-induced desensitization as compared with the sst2(a) receptor. To determine whether a sst2(b) splice variant with similar functional characteristics exists in the rat, we have isolated a cDNA fragment from rat gastric mucosa encoding a sst2(b) receptor and expressed the full-length protein in CHO-K1 cells for functional characterization.2This study provides the first evidence for the occurrence in the rat of the sst2(b) receptor, which has a 15 amino acid carboxy-terminus differing in composition to the 38 amino acid C-terminus of the rat sst2(a) receptor.3In CHO-K1 cells expressing rat recombinant sst2(a) or sst2(b) receptors, SRIF caused concentration-dependent increases in extracellular acidification rates (EAR) with pEC50 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 pEC50 values of 8.3 (sst2(a)) and 8.4 (sst2(b)).4SRIF (3 pM–3 nM) also caused concentration-dependent inhibition of forskolin-stimulated cyclic AMP formation in CHO-sst2(a) cells (pIC50 10.5) and CHO-sst2(b) cells (pIC50 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.5Both 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.6This demonstrates that the operational characteristics of the recombinant rat sst2(a) and sst2(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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Cloning; RT-PCR; somatostatin receptors; splice variants; microphysiometry; adenylate cyclase; sst2(a), sst2(b)
Publisher:	Wiley-Blackwell
ISSN:	1476-5381
Last Modified:	18 Oct 2022 13:39
URI:	https://orca.cardiff.ac.uk/id/eprint/14774

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