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Characterization of ATP receptor which mediates norepinephrine release in PC12 cells

Majid, Mohammed Abdul ; Okajima, Fumikazu ; Kondo, Yoichi

Biochimica et biophysica acta. Molecular cell research, 1992-09, Vol.1136 (3), p.283-289 [Periódico revisado por pares]

Amsterdam: Elsevier B.V

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  • Título:
    Characterization of ATP receptor which mediates norepinephrine release in PC12 cells
  • Autor: Majid, Mohammed Abdul ; Okajima, Fumikazu ; Kondo, Yoichi
  • Assuntos: ATP receptor ; Biological and medical sciences ; Calcium channel ; Cell receptors ; Cell structures and functions ; Fundamental and applied biological sciences. Psychology ; Miscellaneous ; Molecular and cellular biology ; Norepinephrine release ; PC12 cell ; Photoaffinity labeling
  • É parte de: Biochimica et biophysica acta. Molecular cell research, 1992-09, Vol.1136 (3), p.283-289
  • Descrição: PC12 cells, a rat pheochromocytoma cell line, has been reported to release norepinephrine in response to extracellular ATP in the presence of extracellular Ca 2+. The potency order of ATP analogues was adenosin e5′- O-(3-thiotriphosphate) >ATP>adenosine5′-O-(1-thiotriphosphate) = 2-methylthioadenosine5′-triphosphate (MeSATP)> 2′-and3′-O-(4-benzoylbenzoyl)ATP (BzATP)>ADP> 5-adenylylimidodiphosphate. Adenosine 5′- O-(2-thiodiphosphate), β,γ-methyleneadenosine 5′-triphosphate, AMP and adenosine were inactive. The ATP action in the absence of extracellular Ca 2+, suggests a small but appreciable contribution of intracellular Ca 2+ mobilization, for norepinephrine release. However, for some ATP derivatives, like BzATP, almost no contribution of the phospholipase C Ca 2+ pathway is suggested, based on their low activity in inositol phosphates production. To identify the ATP-receptor protein, PC12 cell membranes were photoaffinity-labeled with [ 32P]BzATP. SDS-PAGE analysis showed that a 53-kDa protein labeling was inhibited by ATP and its derivatives, as well as by P 2-antagonists, suramin and reactive blue 2, which inhibit the nucleotide-induced norepinephrine release. The inhibitory activity of the nucleotides was, in parallel with their potency, to induce norepinephrine release. Despite their inability to release norepinephrine, GTP and GTPγS inhibited the BzATP labeling, suggesting the participation of a putative G protein in the ATP-receptor-mediated actions. We suggest that the 53-kDa protein on the PC12 cell surface is an ATP receptor, which mediates the norepinephrine release, depending, mainly, on extracellular Ca 2+ gating.
  • Editor: Amsterdam: Elsevier B.V
  • Idioma: Inglês
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