EFFECTS OF HIRSUTINE, AN ANTIHYPERTENSIVE INDOLE ALKALOID FROM UNCARIA-RHYNCHOPHYLLA, ON INTRACELLULAR CALCIUM IN RAT THORACIC AORTA

The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla (MIQ.) JACKSON, on cytosolic Ca2+ level ([Ca2+]cyt) were studied by using fura-2-Ca2+ fluorescence in smooth muscle of the isolated rat aorta. Noradrenaline and high K+ solution produced a sustained increase in [Ca2+]Cyt. Application of hirsutine after the increases in [Ca2+]Cyt induced by noradrenaline and high K+ notably decreased [Ca2+]Cyt, suggesting that hirsutine inhibits Ca2+ influx mainly through a voltage-dependent Ca2+ channel. Furthermore, the effect of hirsutine on intracellular Ca2+ store was studied by using contractile responses to caffeine under the Ca2+-free nutrient condition in the rat aorta. When hirsutine was added at 30-mu-M before caffeine treatment, the agent slightly but significantly reduced the caffeine-induced contraction. When added during Ca2+ loading, hirsutine definitely augmented the contractile response to caffeine. These results suggest that hirsutine inhibits Ca2+ release from the Ca2+ store and increases Ca2+ uptake into the Ca2+ store, leading to a reduction of intracellular Ca2+ level. It is concluded that hirsutine reduces intracellular Ca2+ level through its effect on the Ca2+ store as well as through its effect on the voltage-dependent Ca2+ channel.