Work

Extracellular nucleotides stimulate receptor-mediated calcium mobilization and inositol phosphate production in human fibroblasts

Year: 1989

Type: article

Abstract: In human skin fibroblasts, low concentrations of extracellular ATP stimulated 45Ca2+ efflux from a slow-turnover intracellular pool, accompanied by inositol phosphate generation. These effects of ATP were not due to a generalized increase in plasma-membrane permeability. The EC50 (concn. giving 50% stimulation) for ATP was dependent on Ca2+ and Mg2+ concentrations in a manner which indicates that a form of ATP uncomplexed with bivalent cations is the active species. The rank order of potency of nucleotides was: ATP = UTP greater than adenosine 5'-[gamma-thio]triphosphate greater than ITP greater than ADP greater than UDP greater than other nucleoside triphosphates. Adenosine 5'-[alpha beta-methylene]triphosphate, adenosine 5'-[beta gamma-methylene]triphosphate and 2-methylthio-ATP were inactive. Thus the nucleotide specificity of this receptor is different from that of previously characterized P2 purinoceptors. Nucleotide-stimulated 45Ca2+ mobilization and inositol phosphate production were markedly inhibited by phorbol ester, and partially inhibited by pertussis-toxin pretreatment. These findings suggest that the coupling of nucleotide receptor to phospholipase C is mediated both by a pertussis-toxin-sensitive G-protein and by a pertussis-toxin-insensitive mechanism.

Source: Biochemical Journal

DOI: 10.1042/bj2630371

Authors: J Fine, P Cole, J S Davidson

Institution: University of Cape Town

Language: English

Topic: Adenosine and Purinergic Signaling

Subfield: Physiology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: bronze

Funders: South African Medical Research Council, University of Cape Town, Medical Research Council

OpenAlex ID: W2208670932