The secretion of cerebrospinal fluid by the epithelial cells of choroid ple
xus is regulated by membrane receptors coupled to adenylyl cyclases or to p
hospholipase C. These intracellular signalling pathways as their interactio
ns were investigated in a sheep choroid plexus cell line. Endothelin-l, bra
dykinin and serotonin induced a transient dose-dependent increase in intrac
ellular calcium. EC 50 were 10(-8)M for endothelin-l, 10(-8) M for bradykin
in and 10(-6) M for serotonin. Maximal increase in intracellular calcium wa
s comparable for bradykinin and serotonin, but was 3 to 5 fold larger for e
ndothelin-l. Successive stimulations with endothelin-1, serotonin or bradyk
inin elicited calcium increases similar to single stimulations reflecting a
bsence of heterologous desensitization between these receptors. Forskolin-i
nduced cAMP accumulation was potentiated by bradykinin, but not by serotoni
n and endothelin-l. This potentiation resulted from an increase in cAMP pro
duction rather than to an inhibition of cAMP hydrolysis. These data suggest
that serotonin, endothelin-l and bradykinin each use specific signalling p
athways in the sheep choroid plexus cells.