TY - JOUR
T1 - Stereoselectivity of butylidenephthalide on voltage-dependent calcium channels in guinea-pig isolated ileum
AU - Ko, Wun-Chang
AU - Sheu, Joen Rong
AU - Leu, Yi Rong
AU - Tzeng, Shu-Huey
AU - Chen, Chi Ming
PY - 1997/11
Y1 - 1997/11
N2 - Two geometric isomers, the Z- and the E- forms, can be separated from synthetic mixtures of butylide-nephthalide (Bdph). Z-Bdph (50-100 μM) non-competitively inhibited Ca2+-induced contractions in depolarized (K+, 60 mM) guinea-pig ileum longitudinal smooth muscle, with a pD2' value of 3.88 ± 0.20 (n = 5). However, E-Bdph (20-100 μM) competitively inhibited these contractions with a pA2 value of 4.56 ± 0.18 (n = 5) which was significantly (P <0.05) greater than the pD2' value of Z-Bdph. In contrast, the two isomers had no stereoselective inhibitory action on Ca2+ influx through pre- or post-junctional membranes of cholinergic nerve endings from which the transmitter acetylcholine is released or on Ca2+ release from intracellular stores. Therefore, the trans-Z and cis-E forms of Bdph might have geometric stereoselectivity for voltage-dependent calcium channels (VDC) in guinea-pig longitudinal smooth muscle. Both isomers might inhibit more selectively the contractile twitch responses evoked by electrical stimulation than by cumulative acetylcholine or carbachol-induced transient contractions in guinea-pig ileum longitudinal smooth muscle.
AB - Two geometric isomers, the Z- and the E- forms, can be separated from synthetic mixtures of butylide-nephthalide (Bdph). Z-Bdph (50-100 μM) non-competitively inhibited Ca2+-induced contractions in depolarized (K+, 60 mM) guinea-pig ileum longitudinal smooth muscle, with a pD2' value of 3.88 ± 0.20 (n = 5). However, E-Bdph (20-100 μM) competitively inhibited these contractions with a pA2 value of 4.56 ± 0.18 (n = 5) which was significantly (P <0.05) greater than the pD2' value of Z-Bdph. In contrast, the two isomers had no stereoselective inhibitory action on Ca2+ influx through pre- or post-junctional membranes of cholinergic nerve endings from which the transmitter acetylcholine is released or on Ca2+ release from intracellular stores. Therefore, the trans-Z and cis-E forms of Bdph might have geometric stereoselectivity for voltage-dependent calcium channels (VDC) in guinea-pig longitudinal smooth muscle. Both isomers might inhibit more selectively the contractile twitch responses evoked by electrical stimulation than by cumulative acetylcholine or carbachol-induced transient contractions in guinea-pig ileum longitudinal smooth muscle.
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U2 - 10.1111/j.2042-7158.1997.tb06053.x
DO - 10.1111/j.2042-7158.1997.tb06053.x
M3 - Article
C2 - 9401949
AN - SCOPUS:0030690226
SN - 0022-3573
VL - 49
SP - 1121
EP - 1125
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
IS - 11
ER -