Effects of calcium antagonists on the evoked release of dynorphin A(1-8) and availability of intraterminal calcium in rat hippocampal mossy fiber synaptosomes

The pharmacological properties of presynaptic calcium (Ca) channels on rat hippocampal mossy fiber synaptosomes were characterized by determining the inhibitory potencies for various classes of Ca antagonists on depolarization-induced Ca mobilization and the release of dynorphin A(1-8)-like immunoreactivity (Dyn-LI). Flunarizine and cinnarizine were the most potent inhibitors of both parameters (IC50 values less than 10(-5) M). Gadolinium and omega-conotoxin (omega-CgTx) were also effective inhibitors of Dyn-LI release (IC50 values less than 3 x 10(-5) M), but omega-CgTx only partially reduced the level of cytosolic free Ca. The release of Dyn-LI was relatively insensitive to both the L-type (dihydropyridines, verapamil and diltiazem) and T-type (amiloride and phenytoin) channel blockers. It appears that presynaptic N-type Ca channels make the most substantial contribution to the Ca influx required for the exocytosis of Dyn-LI from hippocampal mossy fiber nerve endings.