Potent antagonism by BIM-23056 at the human recombinant somatostatin sst5 receptor.
We have investigated the effects of somatostatin (SRIF) and the linear octapeptide BIM-23056 on changes in intracellular calcium ion concentration ([Ca2+]i) and on the formation of inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) in CHO-K1 cells transfected with the human recombinant SRIF sst5 receptor. SRIF elicited concentration-dependent increases in [Ca2+]i, with a pEC50 of 7.02 +/- 0.06, while BIM-23056 (1 x 10(-7) M) behaved not as an agonist but as a potent, surmountable antagonist of these increases in [Ca2+]i. The SRIF concentration-effect curve for increases in [Ca2+]i was shifted rightward producing an estimated pKB for the antagonist of 8.0. BIM-23056 (1 x 10(-7) M) also significantly attenuated Ins(1,4,5)P3 increases due to SRIF, but had no effect on either basal or uridine 5'-triphosphate (UTP) (1 x 10(-4) M) stimulated increases in the levels of [Ca2+]i or Ins(1,4,5)P3.
Wilkinson
G F
GF
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge.
Thurlow
R J
RJ
Sellers
L A
LA
Coote
J E
JE
Feniuk
W
W
Humphrey
P P
PP
D000818:Animals; D016466:CHO Cells / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D011995:Recombination, Genetic; D013004:Somatostatin / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000494:pharmacology
C091737:BIM 23056; D009842:Oligopeptides; D017481:Receptors, Somatostatin; D013004:Somatostatin; D002118:Calcium; D014544:Uridine Triphosphate