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Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP receptors might coexist on endothelial cells. To evaluate this hypothesis, we examined the effects of P2y receptor agonists 2-methylthioadenosine 5'-triphosphate (2MeSATP) and 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) and of UTP on the accumulation of inositol phosphates in bovine aortic endothelial cells. BzATP, 2MeSATP, and UTP produced a smaller maximal effect than ATP. The effects of 2MeSATP and UTP were additive, whereas the effects of ATP and either UTP or 2MeSATP were not. Prior exposure to UTP reduced the subsequent response to UTP to 12% of the control response, whereas the response to 2MeSATP was decreased to 61%. Reciprocally, preincubation with 2MeSATP reduced the subsequent response to 2MeSATP to 23% of the control response, whereas the response to UTP was reduced to 73%. Pertussis toxin pretreatment decreased the response to both ATP and UTP (65% and 70% inhibition, respectively), whereas the response to 2MeSATP was not modified. Our data support the hypothesis that two classes of receptors recognizing ATP are expressed on bovine aortic endothelial cells.

Heterogeneity of ATP receptors in aortic endothelial cells. Involvement of P2y and P2u receptors in inositol phosphate response.