Brooks R R, Jones S M, Moore A F
Proc Soc Exp Biol Med. 1984 Sep;176(4):452-9. doi: 10.3181/00379727-176-41897.
Nolinium bromide inhibits gastric acid secretion and gastrointestinal smooth muscle contraction. While the compound's gastric antisecretory action has been attributed in part to inhibition of gastric adenylate cyclase and the gastric proton-transport ATPase, the mechanism of nolinium bromide's relaxant effect on smooth muscle has not been elucidated. We have determined that nolinium bromide inhibits contraction of vascular smooth muscle, using isolated rabbit aortic strips. This report characterizes the specificity of this inhibition (by using several agonists) and its Ca2+ dependence (by using contractile conditions of known dependence on various Ca2+ pools). Nolinium bromide (50-200 microM) was a reversible, insurmountable inhibitor of contractions induced by Ca2+ (in 40 mM KC1 depolarizing medium) and norepinephrine, with IC50 values of 96 and 118 microM, respectively, for suppression of maximum contractile force. Contractions in response to Asn1Val5-angiotensin II in both 2.5 mM Ca2+ and 0 mM Ca2+ medium were also inhibited (IC50 value = 110 microM under both conditions). Initial contraction rates for all these conditions were depressed by nolinium bromide. Nolinium bromide inhibited equally the phasic (internal Ca2+-dependent) and tonic (external Ca2+-dependent) components of norepinephrine-induced contractions. These results extend the muscle relaxant profile of nolinium bromide to include, albeit with low potency, vascular smooth muscle, and show that its potency is similar in inhibiting the contractile response to three different stimuli: angiotensin II, Ca2+, and norepinephrine.
溴化诺林铵可抑制胃酸分泌和胃肠平滑肌收缩。虽然该化合物的胃抗分泌作用部分归因于对胃腺苷酸环化酶和胃质子转运ATP酶的抑制，但溴化诺林铵对平滑肌松弛作用的机制尚未阐明。我们使用离体兔主动脉条片确定了溴化诺林铵可抑制血管平滑肌收缩。本报告描述了这种抑制作用的特异性（通过使用几种激动剂）及其对Ca2+的依赖性（通过使用已知依赖于各种Ca2+库的收缩条件）。溴化诺林铵（50 - 200 microM）是Ca2+（在40 mM KCl去极化介质中）和去甲肾上腺素诱导收缩的可逆、不可逾越的抑制剂，抑制最大收缩力的IC50值分别为96和118 microM。在2.5 mM Ca2+和0 mM Ca2+介质中，对Asn1Val5 - 血管紧张素II的收缩反应也受到抑制（两种条件下IC50值均为110 microM）。溴化诺林铵降低了所有这些条件下的初始收缩速率。溴化诺林铵同样抑制去甲肾上腺素诱导收缩的相性（内部Ca2+依赖性）和张力性（外部Ca2+依赖性）成分。这些结果扩展了溴化诺林铵的肌肉松弛谱，使其包括血管平滑肌，尽管效力较低，并表明其在抑制对三种不同刺激（血管紧张素II、Ca2+和去甲肾上腺素）的收缩反应方面效力相似。
