Suppression of Cerebrospinal Fluid (CSF) Production by a Na⁺/K⁺Pump Inhibitor Extracted from Human Cerebrospinal Fluid

Abstract

A low molecular weight compound (about 600 daltons) extracted from human cerebrospinal fluid, and sensitive to proteolytic enzymes, has been shown to mimic the specific inhibitory effects of cardiac glycosides on the Na+/K+ pump of erythrocytes. The compound, which was labelled CSF-inhibitor (CSF-I) and reconstituted in artificial rabbit CSF, was used to study its effects on the rate of CSF formation in rabbits. Three groups of adult New Zealand white rabbits of either sex, anesthetized with ketamine and xylazine, and artificially respired were subjected to ventriculocisternal perfusions. Baseline rates of CSF formation were obtained during the first 2 hours of perfusion when plain rabbit CSF was used as the perfusate. Thereafter, the animals were perfused for an additional 2 to 3 hours with either plain rabbits CSF (controls), rabbit CSF containing 10(-6) M ouabain (group 2) or CSF-I (group 3). The rate of CSF formation in control animals was observed to gradually decline with time (about 7.5% in 4 hours). The addition of ouabain to the perfusate caused an abrupt and marked 43% decline in the rate of formation while the addition of CSF-I resulted in a 57% decline. These results suggest that the peptide CSF-I which is present in human CSF may act as an endogenous regulator of CSF production.

Novel roles for y-Protocadherins in the choroid plexus

“…At the apical membrane Na + /K + -ATPase must drive Na + up is electrochemical gradient using ATP and therefore also acts as one of the main drivers of CSF production. This role is supported by studies that show that the inhibition of Na + /K + -ATPase with ouabain leads to a reduced CSF output from the CP (Davson and Segal, 1970;Lorenzo et al, 1989). The action of this pump is also thought to keep the [Na + ] inside the CP epithelial cells to a minimum, which aids in basolateral transport as well.…”