The role of G proteins and related second messenger system on the modulation of acetylcholine release from [3H]choline-preloaded guinea-pig superior cervical ganglion was investigated using the potent general activator NaF. The electrically evoked (1 Hz, 5 min) [3H] release was inhibited by “low” F− concentrations (1-2.5 mM), by the adenylyl cyclase blocker MDL 12330A (10 μM), alone and in combination with 1 mM NaF, and increased by 0.5 mM 8Br-cAMP, 100 μM 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 (1 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 μM 4-aminopyridine and 50 μM tetraethylammonium 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.

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

BORASIO, Pier Giorgio;CERVELLATI, Franco;PAVAN, Barbara;
2004

Abstract

The role of G proteins and related second messenger system on the modulation of acetylcholine release from [3H]choline-preloaded guinea-pig superior cervical ganglion was investigated using the potent general activator NaF. The electrically evoked (1 Hz, 5 min) [3H] release was inhibited by “low” F− concentrations (1-2.5 mM), by the adenylyl cyclase blocker MDL 12330A (10 μM), alone and in combination with 1 mM NaF, and increased by 0.5 mM 8Br-cAMP, 100 μM 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 (1 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 μM 4-aminopyridine and 50 μM tetraethylammonium 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.
2004
Borasio, Pier Giorgio; Cervellati, Franco; Pavan, Barbara; Pareschi, Mc
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/470289
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