Inhibitory effects of tetrahydroisoquinoline derivatives on Ca2+ and Na+ channels in crude nerve endings

Semi-synthetic tetrahydroisoquinoline derivatives prepared from natural alk aloids, possess Ca2+ antagonistic properties. These derivatives significant ly blocked KCl-stimulated Ca2+ uptake (In chick and rat crude nerve endings ) which fan be partially inhibited by the selective N-type Ca2+ channel blo cker omega-conotoxin GVIA or the selective P-type Ca2+ channel blocker omeg a-agatoxin IVA. Moreover, PX42 (10 mu M; for the tetrahydroisoquinoline com pounds in this study) could inhibit the activity of calmodulin-dependent ph osphodiesterase and block veratridine-induced (or tetrodotoxin-sensitive) N a+ uptake. The possible mechanism(s) of non-selective inhibition of ion cha nnels of PX42 is discussed.