Pharmacological Evaluation of Ocoteine, Isolated from Cassytha filiformis, as an α₁-Adrenoceptor Antagonist in Rat Thoracic Aorta

Abstract

Ocoteine, isolated from Cassytha filiformis, was found to be an α₁-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of phenylephrine-induced vasoconstriction (pA₂=7.67±0.09). Removal of endothelium from the aorta did not affect its antagonistic potency (pA₂=7.97±0.07). [³H]-Inositol monophosphate formation caused by noradrenaline (3 μM) was suppressed by ocoteine (10 μM) and prazosin (3 μM). Ocoteine did not affect the contraction induced by U46619, prostaglandin F_2α or angiotensin II, but inhibited slightly those by high K⁺ and endothelin I. Neither the cyclic AMP nor cyclic GMP content of rat thoracic aorta was changed by ocoteine (10 μM). Comparing the EC₅₀ values, the potency of ocoteine against 5-hydroxytryptamine (5-HT) was about 60 times less than that against phenylephrine. Ocoteine (10 μM)also slightly antagonized the clonidine-induced inhibition of the twitch response evoked by field stimulation in rat vas deferens. In guinea pig trachea, the contraction caused by carbachol, histamine, neurokinin A or leukotriene C₄ and β₂-adrenoceptor-mediated relaxing responses induced by isoprenaline were not affected by ocoteine (10 μM). The voltage clamp study in rat ventricular single myocytes revealed that ocoteine (3, 10 μM) inhibited steady state outward currents, but not transient outward currents or slow inward Ca²⁺ currents. It is concluded that ocoteine is a selective α₁-adrenoceptor antagonist in isolated rat thoracic aorta. At high concentrations, it also blocks 5-HT receptors and Na⁺ and steady state outward currents in rat ventricular myocytes.