The Inhibition Effects of Shenmai Injection on Acetylcholine-Induced Catecholamine Synthesis and Secretion by Modulating Nicotinic Acetylcholine Receptor Ion Channels in Cultured Bovine Adrenal Medullary Cells.

Xiting Zhang,Lijuan Chai,Lin Miao,Haoping Mao,Lin Li,Yi Wang,Han Zhang,Shuang Wang,Xiumei Gao

doi:10.1155/2020/8514926

Abstract

Shenmai injection (SMI) has been widely used for the treatment of cardiovascular diseases in China. Cardiovascular disorders are often related to excessive catecholamine (CA) secretion. Here, we report the effects of SMI on CA secretion and synthesis in cultured bovine adrenal medullary cells. We found that SMI significantly reduced CA secretion induced by 300 μM acetylcholine (ACh). Cotreatment with SMI (10 μL/mL) and either of the ACh receptor α-subunit inhibitors, HEX (α3) or DhβE (α4β2), did not produce any further inhibition, indicating that SMI may play a role through α3 and α4β2 channels. Furthermore, SMI reduced tyrosine hydroxylase (TH) activity induced by ACh by inhibiting the phosphorylation of TH at Ser19 and Ser40. TH is phosphorylated at Ser19 by Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) and at Ser40 by protein kinase A (PKA). KN-93 and H89, the antagonists of CaM kinase II and PKA, respectively, inhibited the ACh-induced phosphorylation at Ser19 and Ser40, and the addition of SMI did not augment the inhibitory effect. Taken together, our results show that SMI likely inhibits CA secretion by blocking TH activity at its Ser19 and Ser40 sites.

Highlights

Catecholamines (CAs) are a class of neurotransmitters including norepinephrine (NE), epinephrine (E), and dopamine (DA)
We examined the effect of Shenmai injection (SMI) on CA secretion induced by 300 μM ACh
We found that SMI reduced the CA secretion induced by ACh in adrenal medullary cells, while it had no effect on veratridine and high K+ (HK)-induced catecholamine secretion

Summary

Introduction

Catecholamines (CAs) are a class of neurotransmitters including norepinephrine (NE), epinephrine (E), and dopamine (DA). CAs regulate normal cardiovascular functions at physiological levels, while excessive secretion can aggravate cardiovascular diseases such as heart failure, atherosclerosis, coronary heart disease, hypertension, and so on [1]. Bovine adrenal medullary cells were widely used to detect the effect of various medicines or chemicals on catecholamine secretion and synthesis. Researchers found that there are at least three distinct types of ionic channels that participate in catecholamine secretion, including nicotinic acetylcholine receptor (nAChR) ion channels, voltage-dependent Na+ channels, and voltage-dependent Ca2+ channels [3]. In cultured bovine adrenal medullary cells, Ach and veratridine were reported to be activators of the nicotinic

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