CNS stimulation and PGE2 release. I. Depolarizing agents

Radioimmunoassayable PGE2 was reliably detected in the ventriculocisternal perfusates of chloralose-urethanized cats (557-1481 pg/min; +/- 1 S.E.). Examination of the levels of PGE2 in sequential 30 min samples for periods of up to 6 h revealed that the basal secretion rates of this prostaglandin did not fluctuate ina statistically significant fashion during this extended interval. The addition of either K+ (50 mM) or veratridine (7.5 X 10(-5) M) were shown to reliably evoke a long lasting increase (190-210%) in radioimmunoassayable PGE2 in the ventriculocisternal superfusates. In the majority of experiments, the elevated PGE2 showed a return to prestimulation levels within 60 min after the removal of the depolarizing agent. The ability of two depolarizing agents which act by different mechanisms to produce PGE2 release, and the likelihood that the stimulus-dependent increases were not due to altered clearance, metabolism or dilution makes it likely that the PGE2 levels in the extravascular-extracellular fluid were elevated secondary to increases in neuronal activity.