Microglial calcium responses to platelet-activating factor are inhibited by analogue CAS 99103-16-9 and dihydropyridine PCA 4248 but not by ginkgolide A.
Calcium signals evoked in N9 microglial cells were monitored using the calcium indicator dye Fluo-4 in a fluorescence imaging plate reader. Platelet activating factor in the range 100 nM to 20 microM elicited graded calcium responses. The analogue CAS 99103-16-9 inhibited the evoked calcium rise with an apparent KB of 1.3 +/- 0.4 microM. The dihydropyridine PCA 4248 inhibited the evoked calcium rise with an apparent KB of 1.2 +/- 0.2 microM. Ginkgolide A at concentrations up to 18 microM had no effect on the evoked calcium rise. While CAS 99103-16-9 and PCA 4248 appear to be simple competitive inhibitors of platelet-activating factor responses, the efficacy of ginkgolide in more complex pharmacological situations may result from an action at a site other than the platelet-activating factor receptor.
Ranasinghe
Saman
S
Department of Physiology, University College London, Gower Street, London WC1E 6BT, U.K.
Bolsover
Stephen
S
D000814:Aniline Compounds / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004095:Dihydropyridines / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D046934:Ginkgolides; D005995:Glyceryl Ethers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology*; D006113:United Kingdom; D014966:Xanthenes / Q000378:metabolism
D000814:Aniline Compounds; D004095:Dihydropyridines; D004224:Diterpenes; C409648:Fluo 4; D046934:Ginkgolides; D005995:Glyceryl Ethers; D007783:Lactones; D010972:Platelet Activating Factor; D014966:Xanthenes; C066024:PCA 4248; C073010:1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphono(N,N,N-trimethyl)hexanolamine; C055394:1-palmityl-2-acetylglycerol; D002118:Calcium; C477042:ginkgolide A