Ab. Mackenzie et al., ACTIVATION OF RECEPTOR-OPERATED CATION CHANNELS VIA P-2X1 NOT P-2T PURINOCEPTORS IN HUMAN PLATELETS, The Journal of biological chemistry, 271(6), 1996, pp. 2879-2881
We have investigated the purinoceptor subtypes responsible for calcium
signaling in human platelets, which previous studies have shown to in
volve both Ca2+ influx via receptor-operated cation channels and relea
se of Ca2+ from intracellular stores. Fura-2 measurements of [Ca2+](i)
in stirred platelet suspensions showed that both ADP (40 mu M) and th
e non-hydrolyzable ATP analogue alpha beta-meATP (alpha,beta-methylene
adenosine 5'-triphosphate, 10 mu M) activated a rapid Ca2+ influx wher
eas only ADP mobilized Ca2+ from internal stores. In ''nystatin'' whol
e cell patch clamp recordings, ATP, ADP, and the non-hydrolyzable ATP
analogues, alpha beta-meATP and ATP gamma S (adenosine 5'-O-(3-thiotri
phosphate), all activated a cation channel permeable to both monovalen
t and divalent cations with a single-channel conductance of 11 picosie
mens in NaCl saline. The current response to ATP (40 mu M) was activat
ed within 20 ms and desensitized with a time constant of 47-107 ms in
the continued presence of agonist, which are characteristics of P-2X1
receptors in other tissues. We conclude that human platelets possess a
P-2X1 purinoceptor, which mediates a rapid phase of ADP- or ATP-evoke
d Ca2+ entry via a cation channel, whereas one or more separate ADP-se
lective P-2 purinoceptors evoke release of calcium from intracellular
stores.