Presynaptic inhibition by concanavalin A: are alpha-latrotoxin receptors involved in action potential-dependent transmitter release?
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 microM. 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 alpha2-adrenergic agonist UK 14,304. Inactivation of Gs and Gi/Go 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 alpha-latrotoxin-induced transmitter release, but only when applied before the toxin. The reduction of electrically evoked, as well as alpha-latrotoxin-evoked, release by concanavalin A was attenuated in the presence of glucose and abolished by methyl alpha-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 alpha-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 alpha-latrotoxin receptors may reduce action potential-dependent transmitter release.
Boehm
S
S
Department of Neuropharmacology, University of Vienna, Austria.
Huck
S
S
D000200:Action Potentials / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000502:physiology; D002417:Cattle; D002645:Chickens; D003208:Concanavalin A / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D018000:Receptors, Peptide / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D018377:Neurotransmitter Agents; D011810:Quinoxalines; D018000:Receptors, Peptide; C034800:alpha-latrotoxin receptor; D003208:Concanavalin A; D000068438:Brimonidine Tartrate; D002118:Calcium; D009638:Norepinephrine