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Vol. 56, Issue 6, 1171-1181, December 1999
Neurological and Urological Diseases Research, Abbott Laboratories,
Abbott Park, Illinois
P2X receptors are a family of ATP-gated ion channels. Four cDNAs with a
high degree of homology to the rat P2X2 receptor were isolated from human pituitary and pancreas RNA. Genomic sequence indicated that these cDNAs represent alternatively spliced messages. Northern analysis revealed high levels of human P2X2
(hP2X2) message in the pancreas, and splice variants could
be detected in a variety of tissues. Two cDNAs encoded functional ion
channels when expressed in Xenopus oocytes, a receptor
structurally homologous to the prototype rat P2X2 receptor
(called hP2X2a) and a variant containing a deletion
within its cytoplasmic C terminus (called hP2X2b). Pharmacologically, these functional human P2X2 receptors
were virtually indistinguishable, with the P2X receptor agonists ATP, 2-methylthio-ATP, 2' and
3'-O-(4-benzoylbenzoyl)-ATP, and
ATP5'-O-(3-thiotriphosphate) being approximately
equipotent (EC50 = 1 µM) in eliciting extracellular Ca2+ influx. The P2 receptor agonists 
,
-methylene
ATP, adenosine, adenosine
5'-O-(2-thiodiphosphate), and UTP were inactive
at concentrations up to 100 µM. Both hP2X2a and
hP2X2b receptors were sensitive to the P2 receptor
antagonist pyridoxal-5-phosphate-6-azophenyl-2',4'-disulfonic acid
(IC50 = 3 µM). In contrast to the analogous rat
P2X2 and P2X2b receptors, the desensitization
rates of the hP2X2a and hP2X2b receptors were
equivalent. Both functional forms of the human P2X2
receptors formed heteromeric channels with the human P2X3 receptor. These data demonstrate that the gene structure and mRNA heterogeneity of the P2X2 receptor subtype are
evolutionarily conserved between rat and human, but also suggest that
alternative splicing serves a function other than regulating the
desensitization rate of the human receptor.
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