PDF(Pubmed)
Abstract：
We studied the inhibitory actions of docosahexaenoic acid (DHA) on the contractions induced by carbachol (CCh), angiotensin II (Ang II), and bradykinin (BK) in guinea pig (GP) gastric fundus smooth muscle (GFSM), particularly focusing on the possible inhibition of store-operated Ca2+ channels (SOCCs). DHA significantly suppressed the contractions induced by CCh, Ang II, and BK; the inhibition of BK-induced contractions was the strongest. Although all contractions were greatly dependent on external Ca2+, more than 80% of BK-induced contractions remained even in the presence of verapamil, a voltage-dependent Ca2+ channel inhibitor. BK-induced contractions in the presence of verapamil were not suppressed by LOE-908 (a receptor-operated Ca2+ channel (ROCC) inhibitor) but were suppressed by SKF-96365 (an SOCC and ROCC inhibitor). BK-induced contractions in the presence of verapamil plus LOE-908 were strongly inhibited by DHA. Furthermore, DHA inhibited GFSM contractions induced by cyclopiazonic acid (CPA) in the presence of verapamil plus LOE-908 and inhibited the intracellular Ca2+ increase due to Ca2+ addition in CPA-treated 293T cells. These findings indicate that Ca2+ influx through SOCCs plays a crucial role in BK-induced contraction in GP GFSM and that this inhibition by DHA is a new mechanism by which this fatty acid inhibits GFSM contractions.
摘要：
我们研究了二十二碳六烯酸（DHA）对卡巴胆碱（CCh）引起的收缩的抑制作用，血管紧张素II（AngII），豚鼠（GP）胃底平滑肌（GFSM）中的缓激肽（BK），特别关注存储操作的Ca2+通道(SOCC)的可能抑制。DHA显著抑制CCh诱导的收缩，AngII,和BK；对BK诱导的收缩的抑制作用最强。虽然所有的收缩都很大程度上依赖于外部的Ca2+，超过80％的BK诱导的收缩仍然存在，即使在维拉帕米的存在，电压依赖性Ca2+通道抑制剂。在维拉帕米存在下BK诱导的收缩未被LOE-908（受体操作的Ca2通道（ROCC）抑制剂）抑制，但被SKF-96365（SOCC和ROCC抑制剂）抑制。DHA强烈抑制了在维拉帕米加LOE-908存在下BK诱导的收缩。此外，在维拉帕米加LOE-908的存在下，DHA抑制了环吡嗪酸（CPA）诱导的GFSM收缩，并抑制了由于CPA处理的293T细胞中Ca2添加而引起的细胞内Ca2增加。这些发现表明，通过SOCC流入的Ca2在GPGFSM中BK诱导的收缩中起着至关重要的作用，DHA的这种抑制作用是这种脂肪酸抑制GFSM收缩的新机制。
