title: Stereoselectivity of butylidenephthalide on voltage-dependent calcium channels in guinea-pig isolated ileum.
abstract: Two geometric isomers, the Z- and the E- forms, can be separated from synthetic mixtures of butylidenephthalide (Bdph). Z-Bdph (50-100 microM) non-competitively inhibited Ca(2+)-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 microM) 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.
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical College, Taipei, ROC. wc_ko@mail.tmc.edu.tw
authors.forename: W C
authors.initials: WC
authors.lastname: Ko
authors.forename: J R
authors.initials: JR
authors.lastname: Sheu
authors.forename: Y R
authors.initials: YR
authors.lastname: Leu
authors.forename: S H
authors.initials: SH
authors.lastname: Tzeng
authors.forename: C M
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002217:Carbachol / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000037:antagonists & inhibitors; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D015220:Calcium Channels; D010276:Parasympatholytics; D010277:Parasympathomimetics; D010796:Phthalic Anhydrides; D002217:Carbachol; C026105:butylidenephthalide