Effects of BIBP3226 and BIBP3435 on cytosolic calcium in neuropeptide Y Y1 receptor-transfected Chinese hamster ovary cells and wild type CHO-K1 cells.
The NPY Y1-receptor selective antagonist BIBP3226 exerts a dual control on the cytosolic free calcium concentration ([Ca2+]i) in NPY Y1 receptor-transfected Chinese Hamster Ovary Cells (CHO-Y1 cells). It is a potent inhibitor of the NPY-evoked increase in [Ca2+]i. This can be ascribed to its antagonistic properties for the NPY Y, receptor since its less active stereoisomer, BIBP3435, is much less potent. However, when its concentration exceeds 1 microM, BIBP3226 produces a large increase in [Ca2+]i on its own. This effect is mimicked by BIBP3435 and it also occurs in wild type CHO-K1 cells. These latter cells do not contain high affinity binding sites for [3H]NPY and [3H]BIBP3226 and, hence, no endogenous NPY Y1 receptors. It is concluded that, at moderately high concentrations, the NPY Y1 receptor antagonist BIBP3226 and its entantiomer BIBP3435 are able to increase the [Ca2+ ]i in CHO cells either by stimulating another receptor or by directly affecting cellular mechanisms that are involved in calcium homeostasis.
Van Liefde
Department of Molecular and Biochemical Pharmacology, Free University of Brussels (VUB), Paardenstraat 65, B-1640 Sint-Genesius Rode, Belgium.
Vanderheyden
P M
PM
De Backer
J P
JP
Ebinger
G
G
Vauquelin
G
G
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D009478:Neuropeptide Y / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D013237:Stereoisomerism; D014162:Transfection
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; D002118:Calcium