(±)-Bay K 8644 is a dihydropyridine compound that acts as a specific agonist of L-type calcium channels, with an EC₅₀ value of 17.3nM[1]. (±)-Bay K 8644 promotes calcium influx into cells by increasing the open time of sarcolemmal calcium channels[2]. (±)-Bay K 8644 is widely used to study the role of L-type calcium channels in cardiovascular function, neurotransmission, and cellular signal transduction mechanisms[3]. (±)-Bay K 8644 has been shown to improve hypotension and regulate heart rate[4].
In vitro, treatment of human liver cancer HepG2 cells with (±)-Bay K 8644 (0.1–100nM) for 3–5 days significantly promoted colony formation and cell proliferation[5]. Under partial depolarization conditions induced by 25mM K⁺, a 5-minute treatment of PC12 cells with (±)-Bay K 8644 (10nM–10μM) enhanced the release of [³H]norepinephrine by 5-fold through calcium channel activation, an effect that was calcium-dependent[6].
In vivo, a single intraperitoneal injection of (±)-Bay K 8644 (1mg/kg) administered 1 hour before testing in an LPS-induced depression model in mice significantly improved depressive-like behaviors, reducing immobility time and increasing activity time[7]. In female Wistar rats, a single intraperitoneal injection of (±)-Bay K 8644 (3–5mg/kg) induced a reversible convulsion-like syndrome within 15 minutes[8].
References:
[1] Bechem M, Schramm M. Calcium-agonists. J Mol Cell Cardiol. 1987 May;19 Suppl 2:63-75.
[2] Wu L, Wang R, Karpinski E, et al. Bay K-8644 in different solvents acts as a transient calcium channel antagonist and a long-lasting calcium channel agonist. J Pharmacol Exp Ther. 1992 Mar;260(3):966-73.
[3] Baydoun AR, Markham A, Morgan RM, et al. Bay K 8644, modifier of calcium transport and energy metabolism in rat heart mitochondria: a new intracellular site of action. Br J Pharmacol. 1990 Sep;101(1):15-20.
[4] Barrús MT, Reviriego J, Marín J. Effect of Ca2+ agonist Bay K 8644 in human placental arteries. Gen Pharmacol. 1995 Sep;26(5):989-96.
[5] Yamaguchi M, Murata T, Ramos JW. The calcium channel agonist Bay K 8644 promotes the growth of human liver cancer HepG2 cells in vitro: suppression with overexpressed regucalcin. Mol Cell Biochem. 2020 Sep;472(1-2):173-185.
[6] Albus U, Habermann E, Ferry DR, et al. Novel 1,4-dihydropyridine (Bay K 8644) facilitates calcium-dependent [3H]noradrenaline release from PC 12 cells. J Neurochem. 1984 Apr;42(4):1186-9.
[7] He E, Ma R, Qu S, et al. L-methionine and the L-type Ca2+ channel agonist BAY K 8644 collaboratively contribute to the reduction of depressive-like behavior in mice. Front Neural Circuits. 2024 Aug 29;18:1435507.
[8] Petersen EN. Bay K 8644 induces a reversible spasticity-like syndrome in rats. Eur J Pharmacol. 1986 Nov 4;130(3):323-6.
(±)-Bay K 8644是一种二氢吡啶类化合物，作为特异性的L型钙离子通道激动剂，其EC50值为17.3nM[1]。(±)-Bay K 8644通过增加肌膜钙离子通道的开放时间，从而促进钙离子内流进入细胞[2]。(±)-Bay K 8644被广泛应用于研究L型钙离子通道在心血管功能、神经传递以及细胞信号转导中的作用机制[3]。(±)-Bay K 8644具有改善低血压和调节心率的功能[4]。
在体外，(±)-Bay K 8644（0.1-100nM）处理人肝癌细胞HepG2细胞3-5天，显著促进细胞集落形成和细胞增殖[5]。(±)-Bay K 8644（10nM-10μM）单独处理PC12细胞处理5分钟，在25mM K⁺诱导的部分去极化条件下，(±)-Bay K 8644通过激活钙通道使[³H]去甲肾上腺素的释放增强5倍，且该效应具有钙依赖性[6]。
在体内，(±)-Bay K 8644（1mg/kg）单次腹腔注射处理LPS诱导的抑郁模型小鼠1小时，(±)-Bay K 8644显著改善小鼠的抑郁行为，减少小鼠的不动时间，并增加活动时间[7]。(±)-Bay K 8644（3-5mg/kg）单次腹腔注射处理雌性Wistar大鼠，15分钟内诱导产生可逆性痉挛样综合征[8]。