Inhibitory effects of tetrahydroisoquinoline derivatives on Ca2+ and Na+ channels in crude nerve endings.
Semi-synthetic tetrahydroisoquinoline derivatives prepared from natural alkaloids, possess Ca2+ antagonistic properties. These derivatives significantly blocked KCl-stimulated Ca2+ uptake (In chick and rat crude nerve endings) which can be partially inhibited by the selective N-type Ca2+ channel blocker omega-conotoxin GVIA or the selective P-type Ca2+ channel blocker omega-agatoxin IVA. Moreover, PX42 (10 microM; for the tetrahydroisoquinoline compounds in this study) could inhibit the activity of calmodulin-dependent phosphodiesterase and block veratridine-induced (or tetrodotoxin-sensitive) Na+ uptake. The possible mechanism(s) of non-selective inhibition of ion channels of PX42 is discussed.
Zhang
Y A
YA
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Japan.
Abe
J
J
Wada
T
T
Ichida
S
S
Xu
G Y
GY
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002645:Chickens; D015640:Ion Channel Gating; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007546:Isoquinolines; D015222:Sodium Channels; D020866:omega-Conotoxin GVIA; D010727:Phosphoric Diester Hydrolases; D002118:Calcium