Acetylcholine dramatically increases prostanoid synthesis in piglet parietal cortex

We investigated effects of exogenous acetylcholine on prostanoid synthesis by parietal cortex in neonatal pigs. Cerebrospinal fluid (CSF) with no drug, and CSF containing acetylcholine at 10(-6) to 10(-3) M was injected under a 'closed' cranial window, and after 5 min the CSF was collected and analyzed by radioimmunoassay for prostaglandin (PG) E2, PGF2 alpha, PGD2, 6-keto-PGF1 alpha (the hydrolysis product of prostacyclin), and thromboxane (TX) B2 (the hydrolysis product of TXA2). PGE2 and PGF2 alpha were the predominant prostanoids in CSF under control conditions. Levels of all CSF prostanoids increased after topical application of acetylcholine, with the largest increases being for PGE2 and PGF2 alpha. During control conditions, levels were 1294 +/- 170 (mean +/- S.E.M.) pg/ml for PGE2 (n = 16), 1032 +/- 143 pg/ml for PGF2 alpha (n = 3), 659 +/- 92 pg/ml for 6-keto-PGF1 alpha (n = 15), 141 +/- 44 pg/ml for TXB2 (n = 12), and were below detectable levels for PGD2. Following application of 10(-3) M acetylcholine, levels were 34,535 +/- 5438 pg/ml for PGE2, 15,539 +/- 2772 pg/ml for PGF2 alpha, 2967 +/- 547 pg/ml for 6-keto-PGF1 alpha, 580 +/- 105 pg/ml for TXB2, and 556 +/- 221 pg/ml for PGD2. These results suggest that prostanoids could play a role in mediating effects of acetylcholine in the brain, or in modulating acetylcholine release via a negative feedback mechanism.