Cholecystokinin activates CCKB-receptor-mediated Ca-signaling in hippocampal astrocytes

Cholecystokinin-8S (CCK-8S) is the most abundant neuropeptide in the mammalian cortex and the limbic system; however, its physiological functions remained largely obscure. We studied effects of CCK on astrocytic Ca signaling, which has met considerable interest as a second messenger in astrocytic-neuronal signaling, by digital ratio-imaging of Fura-2/AM loaded rat and mouse hippocampal astrocytes in dissociated culture. Superfusion of CCK-8S (5-50 nM for 2 min) evoked repetitive Ca increases of several hundred nanomolar in a subpopulation of astrocytes. Mouse astrocytes appeared to be more responsive to CCK than rat cells with respect to the fraction of cells responding as well as to the amplitudes of Ca increases. The Ca responses persisted in the absence of extracellular Ca, indicating that release of Ca from intracellular stores is the primary source of these Ca increases. The CCK-8S-induced Ca increases were blocked by the CCKB receptor antagonist PD135158 (100 nM) but not by the CCKA antagonist lorglumide (100 nM). We surmise that astrocytes might be a major primary target for CCK in the CNS.