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 [ 3 H]noradrenaline release by up to 30% with half‐maximal inhibition at 0.16 µ M . Concanavalin A also reduced the release triggered by extracellular Ca 2+ in neurons depolarized by 25 m M K + or rendered Ca 2+ ‐permeable by the ionophore A23187. The inhibitory action of concanavalin A on electrically evoked release was additive to that of the α 2 ‐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 Ca 2+ currents. In contrast, the lectin efficiently blocked both the Ca 2+ ‐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.