Presynaptic inhibition by concanavalin A: Are α-latrotoxin receptors involved in action potential-dependent transmitter release?

Abstract

Effects of concanavalin A on transmitter release were investigated in primary cultures of chick sympathetic neurons. The lectin reduced electrically evoked [3H] noradrenaline release by up to 30% with half- maximal inhibition at 0.16 μM. Concanavalin A also reduced the release triggered by extracellular Ca2+ in neurons depolarized by 25 mM K+ or rendered Ca2+-permeable by the ionophore A23187. The inhibitory action of concanavalin A on electrically evoked release was additive to that of the α2-adrenergic agonist UK 14,304. Inactivation of G(s) and G(i)/G(o) type G proteins by either cholera or pertussis toxin did not alter the inhibitory effect of the lectin. Concanavalin A failed to affect the resting membrane potential, action potential waveforms, or voltage-dependent K+ and Ca2+ currents. In contrast, the lectin efficiently blocked both the Ca2+- dependent and -independent α-latrotoxin-induced transmitter release, but only when applied before the toxin. The reduction of electrically evoked, as well as α-latrotoxin-evoked, release by concanavalin A was attenuated in the presence of glucose and abolished by methyl α-D-mannopyranoside. The dimeric derivative, succinyl-concanavalin A, was significantly less active than tetrameric concanavalin A. In bovine adrenal chromaffin cells, which displayed only weak secretory responses to α-latrotoxin, concanavalin A failed to alter K+ -evoked catecholamine secretion. These results show that concanavalin A causes presynaptic inhibition in sympathetic neurons and indicate that cross-linking of α-latrotoxin receptors may reduce action potential-dependent transmitter release.