Low concentrations of sodium fluoride inhibit neurotransmitter release from the guinea-pig superior cervical ganglion

The role of G proteins and related second messenger system on the modulation of acetylcholine release from [H-3]choline-preloaded guinea-pig superior cervical ganglion was investigated using the potent general activator NaF. The electrically evoked (1 Hz, 5 min) [H-3] re;ease was inhibited by "low" F- concentrations (1-2.5 mM), by the adenylyl cyclase blocker MDL 12330A (10 muM), alone and in combination with 1 mM NaF, and increased by 0.5 mM 8Br-cAMP, 100 muM forskolin and 0.5 mM 3-isobutyl-1-methylxantine. No effect of 1 mM F- was observed on spontaneous release. Fluoride-induced inhibition was counteracted by the G protein blocker sulmazole (I mm), forskolin and alteration of calcium influx by increasing [Ca2+](out) from 2.2 to 6 mM, raising the rate of stimulation (10 Hz, 30 s), or broadening the presynaptic action potential with 10 muM 4-aminopyridine and 50 muM tetraethyl ammonium chloride. Thus a NaF-sensitive G protein, linked to cAMP synthesis, is determinant for the inhibition of neurosecretion in this cholinergic synapse, involving Ca2+-dependent mechanisms. (C) 2003 Elsevier Ireland Ltd. All rights reserved.