Rat somatostatin sst2(a) and sst2(b) receptor isoforms mediate opposite effects on cell proliferation.
We have investigated the actions of somatostatin (SRIF) and angiopeptin on cell proliferation of CHO-K1 cells expressing the recently cloned rat sst2(b) receptor (CHOsst2(b)) and compared these to their effects in cells expressing the sst2(a) receptor (CHOsst2(a)). In contrast to the sst2(a) receptor, the sst2(b) receptor did not mediate inhibition of bFGF (10 ng ml(-1))-stimulated re-growth and cell proliferation. Rather, SRIF (0.1-1000 nM) and angiopeptin (0.1-1000 nM) stimulated basal re-growth and proliferation of CHOsst2(b) cells in a concentration-dependent manner (estimated pEC50 values of 7.8 and 7.9, respectively). The opposite effects of SRIF on cell proliferation mediated through the two sst2 receptor isoforms were both abolished by 18 h pre-treatment with pertussis toxin. The proliferative effect via the sst2(b) receptor was also abolished by the tyrosine kinase inhibitor, genistein. In conclusion, the present study shows that the rat sst2(a) and sst2(b) receptor splice variants mediate opposite effects on cell proliferation.
Alderton
F
F
Glaxo Institute of Applied Pharmacology, University of Cambridge.
Fan
T P
TP
Schindler
M
M
Humphrey
P P
PP
D000818:Animals; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic; D037342:Pertussis Toxin; D051381:Rats; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D006727:Hormone Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; D011993:Recombinant Fusion Proteins; C115977:Sstr2 protein, rat; D010566:Virulence Factors, Bordetella; C106140:somatostatin receptor sst2A; C060347:lanreotide; D016222:Fibroblast Growth Factor 2; D013004:Somatostatin; D037342:Pertussis Toxin