P-type calcium channels are blocked by the alkaloid daurisoline.
IN looking for a structurally defined non-peptide P-channel blocker we have tested the alkaloid daurisoline which has been isolated from traditional Chinese medicinal herb (Menispermum dauricum) used for the treatment of epilepsy, hypertension and asthma. We have found that daurisoline is an inhibitor of omega-Aga-IVA sensitive barium currents in cerebellar Purkinje cells and of excitatory postsynaptic potentials evoked in Purkinje cells by stimulating parallel fibres in acutely prepared cerebellar slices. Daurisoline did not significantly affect omega-Aga-IVA-insensitive barium currents recorded from granule cells freshly isolated from rat cerebellum. Daurisoline passes the blood-brain barrier and will, therefore, facilitate the functional characterization of brain calcium channels as well as the exploration of P-type calcium channels as possible drug targets.
Lu
Y M
YM
Department of Molecular and Cellular Biology, CNS Research, Basle, Switzerland.
Fröstl
W
W
Dreessen
J
J
Knöpfel
T
T
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D066298:In Vitro Techniques; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; C023968:daurisoline