Stereoselectivity of butylidenephthalide on voltage-dependent calcium channels in guinea-pig isolated ileum

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.