Microglial calcium responses to platelet-activating factor are inhibited by analogue CAS 99103-16-9 and dihydropyridine PCA 4248 but not by ginkgolide A.

Abstract

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.