title: The role of nicotinic receptors and calcium channels in mipafox induced inhibition of catecholamine release in bovine chromaffin cells.
abstract: Depolarization induced catecholamine release from chromaffin cells was decreased 28% by N,N'-diisopropyl diamido-phosphorofluoridate (mipafox), an organophosphorus compound (OP) causing neurotoxic effects, while secretion stimulated by nicotinic agonist was inhibited 65%. The reversibility of this effect and the fact that calcium-dependent secretion from digitonin-permeabilized cells was unaffected by mipafox suggest that this compound affects the ionic currents implicated in catecholamine release. Patch-clamp experiments showed that the activity of voltage-dependent calcium channels (VDCC) was inhibited 35% by mipafox being this effect reversible whereas only minor effects were detected on Na(+) and K(+) currents. Finally, we studied the effect of mipafox on nicotinic ionic currents in chromaffin cells. In this case, the OP was able to cause reversible inhibition reaching maximal effects of 50-60%. In conclusion, nicotinic receptors and VDCC should be considered as potential targets in order to understand the neurotoxicity of these chemicals.
authors.forename: L M
authors.initials: LM
authors.lastname: Gutiérrez
authors.forename: M A
authors.initials: MA
authors.lastname: Sogorb
authors.forename: E
authors.initials: E
authors.lastname: Vilanova
authors.forename: S
authors.initials: S
authors.lastname: Viniegra