Effects of the immunosuppressant cyclosporin A on neurotransmitter release from peripheral non-adrenergic, non-cholinergic nerves

Abstract

This study was undertaken to determine the effect of the immunosuppressant cyclosporin A on neurotransmitter release from non-adrenergic, non-cholinergic nerves (tachykininergic nerves) in the rabbit iris sphincter muscle. Cumulative application of cyclosporin A (0.1 to 10 μM) caused a slow onset of contraction in a concentration-dependent manner. Both FK888 (1 μM) and capsaicin (10 μM), a substance P receptor antagonist and a substance P-depleting agent, respectively, inhibited the contractile effect of cyclosporin A, whereas atropine (1 μM) had no effect. Both cyclosporin A and capsaicin (10 μM) stimulated the release of substance P-like immunoreactivity in the iris. Neither the sodium channel blocker tetrodotoxin (1 μM), the N-type voltage-dependent Ca²⁺ channel blocker ω-conotoxin GVIA (1 μM) nor the P-type channel blocker ω-agatoxin IVA (0.2 μM) affected cyclosporin A (1 μM)-induced contraction. In contrast, the L-type Ca²⁺ channel blocker nicardipine (10 μM) inhibited this contractile effect. These results suggest that cyclosporin A stimulates substance P-like tachykinin release by activating L-type voltage-dependent Ca²⁺ channels, resulting in contraction of the rabbit iris sphincter muscle.