p-Chlorobenzyltetrahydroberberine inhibits vascular smooth muscle contractions caused by Ca2+.
OBJECTIVE
To investigate influences of p-chlorobenzyltetrahydroberberine (CPU-86017) and levothyroxin (Lev) on vascular smooth muscle (VSM) contractions by intracellular Ca2+ release and calcium entry.


METHODS
Three kinds of contractions of rat thoracic aortic rings were used to compare suppression by CPU-86017, bepridil (Bep), verapamil (Ver), and nimodipine (Nim) in euthyroid- and Lev-induced hyperthyroidism rats.


RESULTS
The IC50 of CPU-86017 on KCl-induced contractions of euthyroid and hyperthyroid VSM were 80 (36-179) and 121 (62-236) mumol.L-1, respectively. The potency of CPU-86017 was approximate to 1/10 of Bep and 1/100 of Ver and Nim. Suppressions of Ver and Nim on hyperthyroid VSM in Ca(2+)-free solution were greatly attenuated by -86% and -95%, respectively. Slight or no change in activity of CPU-86017 and Bep was found. Contractions on adding Ca2+ into Ca(2+)-free medium were suppressed by CPU-86017 and its potencies in euthyroid and hyperthyroid rats were not different.


CONCLUSIONS
CPU-86017 is more potent to suppress Ca2+ entry than intracellular calcium mobilization and Lev enhances both.
Dai
D Z
DZ
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China. daidz@mailbox.cpu.edu.cn
Jiang
J M
JM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D015764:Bepridil / Q000494:pharmacology; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006980:Hyperthyroidism / Q000139:chemically induced; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013974:Thyroxine; D014700:Verapamil / Q000494:pharmacology
C400084:4-chlorobenzyltetrahydroberberine; D002121:Calcium Channel Blockers; D001599:Berberine; D009553:Nimodipine; D015764:Bepridil; D014700:Verapamil; D013974:Thyroxine; D002118:Calcium