Ca(2+)-channel blockade in rat thoracic aorta by protopine isolated from Corydalis tubers.

The pharmacological properties and mechanism of the action of protopine on isolated rat thoracic aorta were examined. It inhibited norepinephrine (NE, 3 microM)-induced tonic contraction in rat thoracic aorta in a concentration-dependent manner (25-100 micrograms/ml). The phasic contraction caused by NE was inhibited only by a high concentration of protopine (100 micrograms/ml). At the plateau of NE-induced tonic contraction, the addition of protopine also caused relaxation. This relaxing effect of protopine was not antagonized by indomethacin (20 microM) or methylene blue (50 microM), and it still existed in denuded rat aorta or in the presence of nifedipine (2-100 microM). Protopine also inhibited high potassium (60 mM)-induced, calcium-dependent (0.03-3 mM) contraction of rat aorta in a concentration-dependent manner. Neither cAMP nor cGMP level was changed by protopine. Both the formation of inositol monophosphate caused by NE and the phasic contraction induced by caffeine were also not affected by protopine. 45Ca2+ influx caused by either NE or K+ was inhibited by protopine concentration-dependently. It is concluded that protopine relaxed the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.