Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
Pharmacol Res. 2011 Apr;63(4):335-40. doi: 10.1016/j.phrs.2010.12.004. Epub 2010 Dec 17.
Berberine, a natural product alkaloid, has been shown to display a wide array of pharmacological effects. Generally, the mechanism of action of each of these effects has not been well described. The aim of the present study is to test the hypothesis that some of berberine's cardiovascular effects are mediated through activation of cardiac M2 muscarinic cholinergic receptors. In our studies, we tested the ability of berberine to alter the contraction rate of cultured neonatal rodent cardiomyocytes. In these spontaneously contracting primary cultured cells, berberine reduced the contraction rate in a manner independent of β-adrenergic receptor blockade but sensitive to pertussis toxin, a Gi/o G protein inhibitor. Muscarinic antagonists completely blocked the effect of berberine on contraction rate of cardiomyocytes, whereas the effect of berberine was not opposed by antagonists to opioid, adenosine or α-adrenergic receptors. Further, berberine bound to muscarinic receptors of adult mouse heart membranes with relatively high affinity (K(i)=5.4×10(-6)M) comparable to that of the classic muscarinic agonist, carbachol, and to muscarinic M2 receptors exogenously expressed in HEK 293 cells (K(i)=4.9×10(-6)M). Therefore, the findings of the present study suggest that berberine is a muscarinic agonist at M2 receptors, potentially explaining some of its reported cardiovascular effects.
小檗碱是一种天然产物生物碱，已显示出广泛的药理作用。通常，这些作用的作用机制尚未得到很好的描述。本研究旨在检验以下假设，即小檗碱的一些心血管作用是通过激活心脏 M2 毒蕈碱型胆碱能受体来介导的。在我们的研究中，我们测试了小檗碱改变培养的新生啮齿动物心肌细胞收缩率的能力。在这些自发收缩的原代培养细胞中，小檗碱以一种不依赖于β-肾上腺素能受体阻断的方式降低收缩率，但对百日咳毒素敏感，百日咳毒素是一种 Gi/o G 蛋白抑制剂。毒蕈碱拮抗剂完全阻断了小檗碱对心肌细胞收缩率的影响，而阿片受体、腺苷受体或α-肾上腺素受体的拮抗剂并不能拮抗小檗碱的作用。此外，小檗碱与成年小鼠心脏膜上的毒蕈碱受体具有相对较高的亲和力（K(i)=5.4×10(-6)M），与经典毒蕈碱激动剂卡巴胆碱相当，并且与在 HEK 293 细胞中表达的毒蕈碱 M2 受体也有亲和力（K(i)=4.9×10(-6)M）。因此，本研究的结果表明，小檗碱是 M2 受体的毒蕈碱激动剂，可能解释了其一些报道的心血管作用。
