Stereoselectivity of butylidenephthalide on non-adrenergic prejunctional voltage-dependent Ca²⁺ channels in prostatic portion of rat vas deferens

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• 作者：Chung-Hung Shih^a ; Chi-Ming Chen^b ; Wun-Chang Ko^c ; ^{wc_ko@tmu.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：4-Aminopyridine (PubChem CID ; 1727) ; Aspaminol hydrochloride (PubChem CID ; 11971482) ; Butylinenephthalide (PubChem CID ; 642376) ; Diltiazem hydrochloride (PubChem CID ; 62920) ; Noradrenaline bitartrate (PubChem CID ; 297812) ; Verapamil hydrochloride (PubChem CID ; 62969)
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：5 September 2016
• 年：2016
• 卷：786
• 期：Complete
• 页码：47-52
• 全文大小：534 K

文摘

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, 0.2 Hz) 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 Ca²⁺ only partially reversed the twitch inhibition by Z-Bdph, but effectively reversed those by Ca²⁺ channel blockers, such as verapamil, diltiazem and aspaminol, suggesting that the action mechanisms may be different from those of Ca²⁺ channel blockers. K⁺ channel blockers, such as tetraethylammonium (TEA) and 4-aminopyridine (4-AP), may prolong duration of action potential to allow greater Ca²⁺ 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.