"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 [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 microM), alone and in combination with 1 mM NaF, and increased by 0.5 mM 8Br-cAMP, 100 microM 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 microM 4-aminopyridine and 50 microM 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.
Borasio
Pier Giorgio
PG
Department of Biology, Section of General Physiology, University of Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy. brp@unife.it
Cervellati
Franco
F
Pavan
Barbara
B
Pareschi
Maria Cristina
MC
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D004558:Electric Stimulation; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology*; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D007093:Imidazoles; D007097:Imines; D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C014925:RMI 12330A; D012969:Sodium Fluoride; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; C029758:sulmazole; D000109:Acetylcholine; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine