Nucleotides-induced cytosolic calcium transient and plasma membrane permeability in Chang human liver cells

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.