Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Box 980551, Richmond, VA, 23298, USA.
Dig Dis Sci. 2019 May;64(5):1171-1181. doi: 10.1007/s10620-018-5417-5. Epub 2018 Dec 17.
Isovaleric acid (IVA) is a 5-carbon branched-chain fatty acid present in fermented foods and produced in the colon by bacterial fermentation of leucine. We previously reported that the shorter, straight-chain fatty acids acetate, propionate and butyrate differentially affect colonic motility; however, the effect of branched-chain fatty acids on gut smooth muscle and motility is unknown.
To determine the effect of IVA on contractility of colonic smooth muscle.
Murine colonic segments were placed in a longitudinal orientation in organ baths in Krebs buffer and fastened to force transducers. Segments were contracted with acetylcholine (ACh), and the effects of IVA on ACh-induced contraction were measured in the absence and presence of tetrodotoxin (TTx) or inhibitors of nitric oxide synthase [L-N-nitroarginine (L-NNA)] or adenylate cyclase (SQ22536). The effect of IVA on ACh-induced contraction was also measured in isolated muscle cells in the presence or absence of SQ22536 or protein kinase A (PKA) inhibitor (H-89). Direct activation of PKA was measured in isolated muscle cells.
In colonic segments, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion; the IVA response was not affected by TTx or L-NNA but inhibited by SQ22536. Similarly, in isolated colonic muscle cells, ACh-induced contraction was inhibited by IVA in a concentration-dependent fashion and the effect blocked by SQ22536 and H-89. IVA also increased PKA activity in isolated smooth muscle cells.
The branched-chain fatty acid IVA acts directly on colonic smooth muscle and causes muscle relaxation via the PKA pathway.
异戊酸（IVA）是一种 5 碳支链脂肪酸，存在于发酵食品中，并由细菌发酵亮氨酸在结肠中产生。我们之前报道过，较短的直链脂肪酸醋酸盐、丙酸盐和丁酸盐会对结肠运动产生不同的影响；然而，支链脂肪酸对肠道平滑肌和运动的影响尚不清楚。
确定 IVA 对结肠平滑肌收缩性的影响。
将鼠结肠段置于含有 Krebs 缓冲液的器官浴中的纵向位置，并固定在力传感器上。用乙酰胆碱（ACh）收缩段，在无四氧嘧啶（TTx）或一氧化氮合酶抑制剂[L-N-硝基精氨酸（L-NNA）]或腺苷酸环化酶（SQ22536）的情况下测量 IVA 对 ACh 诱导收缩的影响。还在存在或不存在 SQ22536 或蛋白激酶 A（PKA）抑制剂（H-89）的情况下测量了 IVA 对 ACh 诱导收缩的影响。在分离的肌肉细胞中测量了 IVA 对 PKA 的直接激活作用。
在结肠段中，ACh 诱导的收缩被 IVA 以浓度依赖的方式抑制；IVA 反应不受 TTx 或 L-NNA 影响，但被 SQ22536 抑制。同样，在分离的结肠肌肉细胞中，ACh 诱导的收缩也被 IVA 以浓度依赖的方式抑制，并且该作用被 SQ22536 和 H-89 阻断。IVA 还增加了分离的平滑肌细胞中的 PKA 活性。
支链脂肪酸 IVA 直接作用于结肠平滑肌，并通过 PKA 途径引起肌肉松弛。
