Moreland S, Nishimura J, van Breemen C, Ahn H Y, Moreland R S
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543.
Am J Physiol. 1992 Aug;263(2 Pt 1):C540-4. doi: 10.1152/ajpcell.1992.263.2.C540.
Norepinephrine (NE) plus guanosine triphosphate (GTP) increases myofilament Ca2+ sensitivity in alpha-toxin-permeabilized smooth muscle. We used alpha-toxin-permeabilized rabbit mesenteric arteries to determine the temporal relationships among force, myosin light chain (MLC) phosphorylation, stiffness, and shortening velocity during contractions in response to Ca2+ alone and to the same [Ca2+] in the presence of NE plus GTP. The addition of NE plus GTP caused a marked increase in the tonic contraction but only transiently elevated the level of MLC phosphorylation over that observed in the presence of Ca2+ alone. NE plus GTP induced similar increases in force and stiffness, but shortening velocity depended solely on the [Ca2+]. A regulated MLC phosphatase could explain the initial increase in force and MLC phosphorylation, but not the maintenance of enhanced force while MLC phosphorylation levels fell to values similar to those in response to Ca2+ alone. Therefore, additional elements must be involved in the maintenance of the receptor and G protein-dependent increase in myofilament Ca2+ sensitivity.
去甲肾上腺素(NE)加三磷酸鸟苷(GTP)可增加α-毒素通透的平滑肌中肌丝对Ca2+的敏感性。我们使用α-毒素通透的兔肠系膜动脉来确定在单独对Ca2+以及在NE加GTP存在下对相同[Ca2+]的收缩过程中,力、肌球蛋白轻链(MLC)磷酸化、硬度和缩短速度之间的时间关系。添加NE加GTP导致强直收缩显著增加,但仅短暂提高了MLC磷酸化水平,高于单独存在Ca2+时观察到的水平。NE加GTP诱导力和硬度出现类似增加,但缩短速度仅取决于[Ca2+]。一种受调节的MLC磷酸酶可以解释力和MLC磷酸化的初始增加,但无法解释在MLC磷酸化水平降至与单独对Ca2+反应时相似的值时增强力的维持情况。因此,在维持受体和G蛋白依赖性的肌丝Ca2+敏感性增加方面,必然涉及其他因素。