Treatment of Fura-2 loaded HEL cells, a human megakaryocyte-like cell
line, with P2-purinoceptor nucleotide ligands (ADP, ATP, UTP, 2-methyl
thio-ATP) evoked a rise in cytosolic calcium. Homologous- and cross-de
sensitization studies using sequential addition of nucleotides showed
that the ADP-induced calcium response in HEL cells was mediated mainly
by purinoceptor(s) for which ADP but not ATP was an agonist. There we
re also minor contributions for purinoceptors for which ATP and ADP ar
e both agonists (probably P2U and P2Y). ATP inhibited the ADP-induced
calcium response in HEL cells. This inhibition was overcome by raising
the ADP concentration, thus indicating that ATP was an antagonist for
the HEL cell ADP receptor. AMP was also an antagonist, albeit weak, f
or the HEL cell ADP receptor. Antagonism of the ADP-induced calcium re
sponse by ATP was similarly observed in MEG-01 cells, another human me
gakaryocyte-like cell line, but not in 293 cells, a nonhematopoietic c
ell line. These studies suggest that HEL cells express and ADP recepto
r for which ATP and AMP are antagonists. This characteristic of the HE
L cell ADP receptor is also displayed by the platelet P2T. Thus, HEL c
ells appear to be a surrogate source of the platelet ADP receptor.