Ching-Wei Chang (1), Feng-Nien Ko (1), Ming-Jai Su (1), Yang-Chang Wu
(2) and Che-Ming Teng (1,*)
(1) Pharmacological Institute, College of Medicine, National Taiwan University,
No.1, Jen-Ai Rd., 1st Section, Taipei 10018, Taiwan
(2) Graduate Institute of Natural Products, Kaohsiung Medical College, Kaohsiung
807, Taiwan
(*) To whom correspondence should be addressed.
Abstract: Ocoteine, isolated from Cassytha filiformis, was found
to be an alpha1-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 microM) was suppressed by ocoteine
(10 microM) and prazosin (3 microM). Ocoteine did not affect the contraction
induced by U-46619, prostaglandin F2alpha 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 microM). Comparing
the EC50 values, the potency of ocoteine against 5-hydroxytryptamine (5-HT)
was about 60 times less than that against phenylephrine. Ocoteine (10 microM)
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 beta2-adrenoceptor-mediated relaxing responses induced
by isoprenaline were not affected by ocoteine (10 microM). The voltage clamp
study in rat ventricular single myocytes revealed that ocoteine (3, 10 microM)
inhibited steady state outward currents, but not transient outward currents
or slow inward Ca2+ currents. It is concluded that ocoteine is a selective
alpha1-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.
Keywords: alpha1-Adrenoceptor antagonist, Ocoteine, Thoracic aorta (rat),
Cassytha filiformis