PMID- 8159738
OWN - NLM
STAT- MEDLINE
DCOM- 19940516
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 91
IP  - 8
DP  - 1994 Apr 12
TI  - Cloning and expression of a human P2U nucleotide receptor, a target for cystic 
      fibrosis pharmacotherapy.
PG  - 3275-9
AB  - The Cl- secretory pathway that is defective in cystic fibrosis (CF) can be 
      bypassed by an alternative pathway for Cl- transport that is activated by 
      extracellular nucleotides. Accordingly, the P2 receptor that mediates this effect 
      is a therapeutic target for improving Cl- secretion in CF patients. In this 
      paper, we report the sequence and functional expression of a cDNA cloned from 
      human airway epithelial (CF/T43) cells that encodes a protein with properties of 
      a P2U nucleotide receptor. With a retrovirus system, the human airway clone was 
      stably expressed in 1321N1 astrocytoma cells, a human cell line unresponsive to 
      extracellular nucleotides. Studies of inositol phosphate accumulation and 
      intracellular Ca2+ mobilization induced by extracellular nucleotides in 1321N1 
      cells expressing the receptor identified this clone as the target receptor in 
      human airway epithelia. In addition, we independently isolated an identical cDNA 
      from human colonic epithelial (HT-29) cells, indicating that this is the same P2U 
      receptor that has been functionally identified in other human tissues. Expression 
      of the human P2U receptor (HP2U) in 1321N1 cells revealed evidence for autocrine 
      ATP release and stimulation of transduced receptors. Thus, HP2U expression in the 
      1321N1 cell line will be useful for studying autocrine regulatory mechanisms and 
      in screening of potential therapeutic drugs.
FAU - Parr, C E
AU  - Parr CE
AD  - Division of Pulmonary Diseases, University of North Carolina, Chapel Hill 
      27599-7020.
FAU - Sullivan, D M
AU  - Sullivan DM
FAU - Paradiso, A M
AU  - Paradiso AM
FAU - Lazarowski, E R
AU  - Lazarowski ER
FAU - Burch, L H
AU  - Burch LH
FAU - Olsen, J C
AU  - Olsen JC
FAU - Erb, L
AU  - Erb L
FAU - Weisman, G A
AU  - Weisman GA
FAU - Boucher, R C
AU  - Boucher RC
FAU - Turner, J T
AU  - Turner JT
LA  - eng
SI  - GENBANK/U07225
GR  - DE07389/DE/NIDCR NIH HHS/United States
GR  - GM36887/GM/NIGMS NIH HHS/United States
GR  - HL34322/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Chloride Channels)
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Inositol Phosphates)
RN  - 0 (P2RY2 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Receptors, Purinergic P2Y2)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 8Y164V895Y (Carbachol)
RN  - SY7Q814VUP (Calcium)
RN  - UT0S826Z60 (Uridine Triphosphate)
SB  - IM
EIN - Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):13067. PMID: 7809171
MH  - Adenosine Triphosphate/pharmacology
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Calcium/metabolism
MH  - Carbachol/pharmacology
MH  - Chloride Channels/*genetics
MH  - Cloning, Molecular
MH  - DNA Primers/chemistry
MH  - DNA, Complementary/genetics
MH  - Gene Expression
MH  - Genes
MH  - Humans
MH  - Inositol Phosphates/metabolism
MH  - Molecular Sequence Data
MH  - RNA, Messenger/genetics
MH  - Receptors, Cell Surface/*genetics
MH  - Receptors, Purinergic P2/*genetics/metabolism
MH  - Receptors, Purinergic P2Y2
MH  - Signal Transduction
MH  - Tissue Distribution
MH  - Uridine Triphosphate/pharmacology
PMC - PMC43559
EDAT- 1994/04/12 00:00
MHDA- 1994/04/12 00:01
PMCR- 1994/10/12
CRDT- 1994/04/12 00:00
PHST- 1994/04/12 00:00 [pubmed]
PHST- 1994/04/12 00:01 [medline]
PHST- 1994/04/12 00:00 [entrez]
PHST- 1994/10/12 00:00 [pmc-release]
AID - 10.1073/pnas.91.8.3275 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3275-9. doi: 10.1073/pnas.91.8.3275.