PMID- 10448933
OWN - NLM
STAT- MEDLINE
DCOM- 19990908
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 377
IP  - 1
DP  - 1999 Jul 14
TI  - A novel biological role for prostaglandin D2 is suggested by distribution studies
      of the rat DP prostanoid receptor.
PG  - 101-15
AB  - We report the cloning, functional expression and cell-specific localization of
      the rat homologue of the prostaglandin D2 receptor (DP). In situ hybridization,
      utilizing multiple digoxigenin-labelled riboprobes and their complementary sense 
      controls, was performed to determine the detailed distribution of DP receptor
      mRNA in the central nervous system and the gastrointestinal tract. Within the
      brain, the leptomeninges and choroid plexus expressed DP receptor mRNA.
      Transcripts detected in the spinal cord were localized to the sensory and motor
      neurons of the dorsal and ventral horns, respectively, suggesting a role for the 
      DP receptor in the modulation of central nervous system processes, including pain
      transmission. Within the gastrointestinal tract (stomach, duodenum, ileum and
      colon) signals were highly localized to the mucous-secreting goblet cells and the
      columnar epithelium. These findings suggest a novel biological role for
      prostaglandin D2-mediated activity at the DP receptor, namely mucous secretion.
      In addition, radioligand binding assays (saturation analyses and equilibrium
      competition assays) and functional assays (measuring cAMP accumulation) were
      performed to characterize the recombinant rat DP receptor expressed in human
      embryonic kidney (HEK) 293(EBNA) cells. A single site of binding (K(D) = 14 nM,
      Bmax = 115 fmol/mg protein) was measured for prostaglandin D2-specific binding to
      the rat DP receptor. Prostaglandin D2 proved to be a potent agonist at the rat DP
      receptor (EC50 = 5 nM). The rank order of efficacy for DP receptor specific
      agonists [prostaglandin D2 = prostaglandin J2 = BW 245C
      (5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropylhydantoin)) > L-644,698
      ((4-(3-(3-(3-hydroxyoctyl)-4-oxo-2-thiazolidinyl) propyl) benzoic acid)
      (racemate)] reflected the affinity with which the ligands bound to the receptor.
FAU - Wright, D H
AU  - Wright DH
AD  - Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec,
      Canada.
FAU - Nantel, F
AU  - Nantel F
FAU - Metters, K M
AU  - Metters KM
FAU - Ford-Hutchinson, A W
AU  - Ford-Hutchinson AW
LA  - eng
SI  - GENBANK/AF120101
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Epitopes)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptides)
RN  - 0 (RNA Probes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Prostaglandin)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 98849-88-8 (FLAG peptide)
RN  - E0399OZS9N (Cyclic AMP)
RN  - RXY07S6CZ2 (Prostaglandin D2)
RN  - XZF106QU24 (prostaglandin D2 receptor)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding, Competitive
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - Cloning, Molecular
MH  - Cyclic AMP/biosynthesis
MH  - Epitopes
MH  - Gene Expression
MH  - Humans
MH  - In Situ Hybridization
MH  - Molecular Sequence Data
MH  - Oligopeptides
MH  - Peptides/genetics
MH  - Prostaglandin D2/*physiology
MH  - RNA Probes
MH  - RNA, Messenger/genetics/metabolism
MH  - Radioligand Assay
MH  - Rats
MH  - *Receptors, Immunologic
MH  - Receptors, Prostaglandin/genetics/*metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Tissue Distribution
EDAT- 1999/08/17 00:00
MHDA- 1999/08/17 00:01
CRDT- 1999/08/17 00:00
PHST- 1999/08/17 00:00 [pubmed]
PHST- 1999/08/17 00:01 [medline]
PHST- 1999/08/17 00:00 [entrez]
AID - S0014-2999(99)00358-1 [pii]
AID - 10.1016/s0014-2999(99)00358-1 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1999 Jul 14;377(1):101-15. doi: 10.1016/s0014-2999(99)00358-1.