P2 purinergic receptors and cellular calcium metabolism in A 431 human epidermoid carcinoma cells.
Stimulation of P2 purinergic receptors on A 431 human epidermoid cells with ATP rapidly mobilized intracellular calcium and increased cytosolic free Ca2+ ([Ca2+]i). Incorporation of 45Ca2+ was also stimulated by ATP at a rate less than that of [Ca2+]i elevation. Among a number of nucleosides, nucleotides, and their analogues examined, ATP, GTP, UTP, ADP, UDP, adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), and 5'-adenylylimidodiphosphate (AMP-PNP) increased both [Ca2+]i and 45Ca2+ influx, whereas others did not; these latter two analogues (ATP gamma S and AMP-PNP) blocked the ATP-stimulated 45Ca2+ influx only very slightly, suggesting that they are not prominent antagonists but rather agonists. A high correlation between [Ca2+]i increase and 45Ca2+ influx, in terms of nucleotide specificity, suggests the involvement of [Ca2+]i in influx of 45Ca2+. It appeared that [Ca2+]i elevated by several nucleotides or nucleotide analogues opened a calcium gate, thus allowing the influx of 45Ca2+. P2 purinergic receptors on these cells had such a characteristic that they were rapidly desensitized. These nucleotides or analogues also affected epidermal growth factor (EGF) receptors by inhibiting the EGF binding. The differences of ligand or substrate specificities between P2 purinergic receptors and ecto-nucleotidases indicates that the two components are different molecules involved in different systems.
Hosoi
K
K
Department of Oral Physiology, Meikai University School of Dentistry, Saitama, Japan.
Fujishita
M
M
Sugita
K
K
Kurihara
K
K
Atsumi
T
T
Murai
T
T
Ueha
T
T
D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002294:Carcinoma, Squamous Cell; D004533:Egtazic Acid / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009705:Nucleosides / Q000378:metabolism / Q000494:pharmacology; D009708:Nucleotidases / Q000378:metabolism; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*; D012265:Ribonucleotides / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002132:Calcium Radioisotopes; D009705:Nucleosides; D011983:Receptors, Purinergic; D012265:Ribonucleotides; D004533:Egtazic Acid; D066246:ErbB Receptors; D009708:Nucleotidases; D002118:Calcium