Effects of extracellular nucleotides on single cells and populations of human osteoblasts: contribution of cell heterogeneity to relative potencies

Abstract

1. Human osteoblasts responded to the application of extracellular nucleotides, acting at P₂-receptors, with increases in cytosolic free calcium concentration ([Ca²⁺]_i).

2. In populations of human osteoblasts, adenosine 5′-diphosphate (ADP) evoked a rise in [Ca²⁺]_i with less than 40% of the amplitude of that induced by adenosine 5′-triphosphate (ATP).

3. ATP and uridine 5′-triphosphate (UTP) were applied to single human osteoblasts and induced [Ca²⁺]_i rises of comparable amplitude in every cell tested.

4. However, from the results of single cell studies with ADP (and 2-methylthioATP (2-meSATP)) two groups of cells were delineated: one group responded to ADP (or 2-meSATP) with a rise in [Ca²⁺]_i indistinguishable from that evoked by ATP; whereas the second group failed completely to respond to ADP (or 2-meSATP).

5. Therefore heterogeneity of receptor expression exists within this population of human osteoblasts. The limited distribution of the ADP-responsive receptor underlies the small response to ADP, compared with ATP, recorded in populations of human osteoblasts. This heterogeneity may reflect differences in the differentiation status of individual cells.

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