Vasoactive amine responses in murine cerebrovascular endothelial cells as measured by extracellular acidification rates

The Cytosensor(TM) microphysiometer device is capable detecting cellular re sponses to specific bioactive ligands by measuring the extracellular acidif ication rate (ECAR). Using microphysiometry, we were able to determine that cerebovascular endothelial cells derived from SJL/J mice were more sensiti ve to serotonin (maximal ECAR response at 100 nM), whereas BALB/c-derived c erebrovascular endothelial cells (CVE) were relatively insensitive (maximal ECAR response at 30 mu M). Serotonin (5HT)(1) and 5HT(2) receptor antagoni sts inhibited the serotonin-mediated increases in ECAR. The cells' response s to histamine in both strains were similar (maximal ECAR required 100 mu M Of histamine). H-1 and H-3 receptor subtype antagonists specifically inhib ited the histamine responses. Bradykinin also revealed sensitivity differen ces in that maximal ECAR changes for CVE from SJL/J mice could be observed with 1 mu M, as compared to the ECAR responses from BALB/c mice CVE, which required 10 mu M. Exposure to bradykinin antagonists revealed that the resp onse was due to the stimulation of B-2 receptors. These microphysiometry re sults reveal that the cerebrovascular endothelial cells of SJL/J mice tend to be more sensitive to vasoactive substances than those of BALB/c mice. (C ) 2000 Wiley-Liss, Inc.