Holmuhamedov E L, Bacon J A, Ulrich R G
Upjohn Laboratories, Kalamazoo, MI 49007, USA.
Biochem Mol Biol Int. 1995 Mar;35(3):595-604.
Extracellular nucleotides induce changes in cytosolic free Ca++ and also increase plasma membrane permeability to Ca++ ions in Chang human liver cells. Ca++ permeability induced by nucleotides is reversible and inactivated immediately upon removal of agonist. Stimulated cells transferred into the fresh medium and re-exposed to nucleotides demonstrate reopening of Ca++ channel without stimulation of Ca++ transient. Relative potencies of nucleotides to induce membrane permeability and Ca++ transient were: UTP > ATP > gamma-S-ATP > ADP (non-hydrolyzable ATP analogues and AMP had no effect). The permeability is not affected by specific inhibitors of voltage-operated calcium channels (verapamyl,cis-diltiazem and nifedipin). Nucleotides do not produce plasma membrane damages at concentrations up to 1 mM, as shown by exclusion of the propidium iodide. There are at least two types of nucleotides receptors in Chang cell membrane: P2y subtype receptors which is responsible for generation of the Ca++ transient, and P2x subtype receptors which lead to the opening of plasma membrane Ca++ channels upon activation.
细胞外核苷酸可诱导Chang人肝细胞胞质游离钙离子浓度发生变化,还可增加质膜对钙离子的通透性。核苷酸诱导的钙离子通透性是可逆的,去除激动剂后立即失活。将受刺激的细胞转移到新鲜培养基中并再次暴露于核苷酸时,钙离子通道会重新开放,而不会刺激钙离子瞬变。核苷酸诱导膜通透性和钙离子瞬变的相对效力为:UTP > ATP > γ-S-ATP > ADP(不可水解的ATP类似物和AMP无作用)。通透性不受电压门控钙通道特异性抑制剂(维拉帕米、顺式地尔硫䓬和硝苯地平)的影响。如碘化丙啶排斥实验所示,核苷酸在浓度高达1 mM时不会造成质膜损伤。Chang细胞膜中至少有两种类型的核苷酸受体:负责产生钙离子瞬变的P2y亚型受体,以及激活后导致质膜钙离子通道开放的P2x亚型受体。