title: Stereoselectivity of butylidenephthalide on non-adrenergic prejunctional voltage-dependent Ca(2+) channels in prostatic portion of rat vas deferens.
abstract: The naturally occurring and synthetic butylinenephthalide (Bdph) has two geometric isomers. Z- and E-Bdph were reported to have geometric stereoselectivity for voltage-dependent calcium channels (VDCCs) in guinea-pig ileum. The aim of this study was to investigate whether the binding of Z- and E-Bdph on prejunctional VDCCs of rat vas deferens (RVD) is stereoselective. The twitch responses to electrical field stimulation (EFS, supramaximal voltage, 1 ms, 0.2Hz) were recorded on a polygraph. Z- and E-Bdph concentration-dependently inhibited the twitch responses to EFS in full tissue, prostatic portion and epididymal portion of RVD. The pIC50 value of Z-Bdph was greater than that of E-Bdph in the electrically stimulated prostatic portion of RVD, suggesting that the binding of Bdph on the non-adrenergic prejunctional VDCCs of cell membrane is stereoselective. In the prostatic portion, exogenous Ca(2+) only partially reversed the twitch inhibition by Z-Bdph, but effectively reversed those by Ca(2+) channel blockers, such as verapamil, diltiazem and aspaminol, suggesting that the action mechanisms may be different from those of Ca(2+) channel blockers. K(+) channel blockers, such as tetraethylammonium (TEA) and 4-aminopyridine (4-AP), may prolong duration of action potential to allow greater Ca(2+) entry and induced more release of transmitters. Therefore both blockers via their prejunctional actions reversed the twitch inhibition induced by Z-Bdph in all preparations of RVD by a non-specific antagonism.
authors.affiliation: Division of Thoracic Medicine, Department of Internal Medicine, School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan.
authors.forename: Chung-Hung
authors.initials: CH
authors.lastname: Shih
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan. Electronic address: wc_ko@tmu.edu.tw.
authors.forename: Wun-Chang
authors.initials: WC
authors.lastname: Ko
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009068:Movement / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010796:Phthalic Anhydrides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011467:Prostate; D051381:Rats; D013237:Stereoisomerism; D013379:Substrate Specificity; D019789:Tetraethylammonium / Q000494:pharmacology; D014649:Vas Deferens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology
chemical_list: D015220:Calcium Channels; D010796:Phthalic Anhydrides; D019789:Tetraethylammonium; D015761:4-Aminopyridine; C026105:butylidenephthalide; D002118:Calcium; D009638:Norepinephrine
keywords: 4-Aminopyridine (PubChem CID: 1727); Aspaminol hydrochloride (PubChem CID: 11971482); Butylinenephthalide (Bdph); Butylinenephthalide (PubChem CID: 642376); Diltiazem hydrochloride (PubChem CID: 62920); Noradrenaline bitartrate (PubChem CID: 297812); Potassium channel blockers; Rat vas deferens; StereoSelectivity; TwiTch response; Verapamil hydrochloride (PubChem CID: 62969); Voltage-dependent calcium channels