Inhibition of Ca2+‐regulated exocytosis by levetiracetam in guinea‐pig antral mucous cells: role of synaptic vesicle protein 2A, SV2A

Abstract

Levetiracetam, an antiepileptic drug, a ligand for the SV2A, which contributes the priming of synaptic vesicles for neurotransmitter release. In this study, we investigated the effects of levetiracetam on Ca2+‐regulated exocytosis activated by acetylcholine (ACh) in antral mucous cells of guinea pigs. Because the priming dependent on ATP is the final step for releasing granular contents in the antral mucous cells. The Ca2+‐regulated exocytosis in isolated antral mucous cells was observed by videomicroscopy. Dinitrophenol (DNP) inhibits the priming resulting in a decrease in the frequency of Ca2+‐regulated exocytosis and 8‐bromoguanosine 3′, 5′‐cyclic monophosphate (8BrcGMP) enhances the priming resulting in an increase in its frequency. Levetiracetam inhibited the frequency of Ca2+‐regulated exocytosis by 40%, but it had no effects on the frequency in DNP‐treated cells. When we first added levetiracetam and then 8BrcAMP, 8BrcAMP did not enhance the frequency of Ca2+‐regulated exocytosis. In the next, when we first added 8BrcGMP and then levetiracetam, 8BrcGMP still enhanced the frequency. These results suggest that levetiracetam inhibits the priming of Ca2+‐regulated exocytosis in antral mucous cells. In conclusion, in antral mucous cells, the SV2A, which exists on the mucous granules, plays a crucial role in the priming.