EVIDENCE FOR A DISCRETE UTP RECEPTOR IN CARDIAC ENDOTHELIAL-CELLS

1 We have examined the effects of various purine and pyrimidine nucleo tides upon cells cultured from guinea-pig cardiac endothelium (CEC), a nd find the P-2Y-agonist 2-methylthioadenosine triphosphate (2MeSATP) to be a potent (EC(50)=85+/-10.2. nM) stimulator of increases in intra cellular calcium concentrations, while uridine 5'-triphosphate (UTP) a nd adenosine 5'-triphosphate (ATP) are less potent but equipotent with one another (EC(50)s=2.1+/-0.3 and 1.8+/-0.2 mu M, respectively). 2 W hile the P-2Y receptor exhibited rapid homologous desensitization, thi s had no effect upon subsequent responsiveness of CEC to either ATP or UTP. Effects of maximal concentrations of ATP and UTP were not only a dditive, but did not cross-desensitize. Responses to UTP (but not to A IP or 2MeSATP) were blocked by treatment with pertussis toxin (PTX); a il three nucleotides appeared to liberate calcium from an intracellula r pool. 3 Suramin (30 mu M) significantly (P<0.05) increased the EC(50 ) for ATP-dependent increases in intracellular calcium (5.3+/-2.2 mu M vs. 2.0+/-0.9 mu M in the absence of suramin). while it completely bl ocked the response to 2MeSATP. Suramin had no effect upon responses to UTP at concentrations of 100 mu M. 4 We conclude that in addition to the P-2Y and P-2U subtypes of the ATP receptor. an additional receptor responsive to UTP but exhibiting no affinity for purine nucleotides i s present in CEC; this pyrimidine receptor' liberates intracellular ca lcium via a G-protein, and may partly mediate the contractile response to UTP in the coronary vasculature.