This study demonstrates the localization of the prostaglandin (PG)D2 receptor (DP) within the mucous‐secreting globlet cells of the human colon by in situ hybridization, which suggests a role for DP in mucous secretion. Selective high affinity ligands were used, therefore, to evaluate DP regu...
This study demonstrates the localization of the prostaglandin (PG)D2 receptor (DP) within the mucous‐secreting globlet cells of the human colon by in situ hybridization, which suggests a role for DP in mucous secretion. Selective high affinity ligands were used, therefore, to evaluate DP regulation of mucous secretion in LS174T human colonic adenocarcinoma cells.The expression of hDP in LS174T cells was confirmed at the mRNA level by reverse transcriptase‐polymerase chain reaction, and at the protein level by radioligand binding assays and signal transduction (cyclic AMP accumulation) assays. PGD2 and the highly selective DP‐specific agonist L‐644,698 ((4‐(3‐(3‐(3‐hydroxyoctyl)‐4‐oxo‐2‐thiazolidinyl) propyl) benzoic acid) (racemate)), but not PGE2 competed for [3H]‐PGD2‐specific binding to LS174T cell membranes (Ki values of 0.4 nM and 7 nM, respectively). The DP‐specific agonists PGD2, PGJ2, BW245C (5‐(6‐carboxyhexyl)‐1‐(3‐cyclohexyl‐3‐hydroxypropylhydantoin)), and L‐644,698 showed similar potencies in stimulating cyclic AMP accumulation (EC50 values: 45-90 nM) and demonstrated the expected rank order of potency. PGE2 also elicited cyclic AMP production in this cell line (EC50 value: 162 nM).The activation of cyclic AMP production by PGD2 and L‐644,698, but not PGE2, was inhibited by the selective DP antagonist BW A868C. Thus, PGD2 and L‐644,698 act through hDP in LS174T cells. PGD2, L‐644,698 and PGE2 (an established mucin secretagogue) potently stimulated mucin secretion in LS174T cells in a concentration‐dependent manner (EC50<50 nM). However, BW A868C effectively antagonized only the mucin secretion mediated by PGD2 and L‐644,698 and not PGE2. These data support a role for the DP receptor in the regulation of mucous secretion.British Journal of Pharmacology (2000) 131, 1537-1545; doi:10.1038/sj.bjp.0703688
This study demonstrates the localization of the prostaglandin (PG)D2 receptor (DP) within the mucous‐secreting globlet cells of the human colon by in situ hybridization, which suggests a role for DP in mucous secretion. Selective high affinity ligands were used, therefore, to evaluate DP regulation of mucous secretion in LS174T human colonic adenocarcinoma cells.The expression of hDP in LS174T cells was confirmed at the mRNA level by reverse transcriptase‐polymerase chain reaction, and at the protein level by radioligand binding assays and signal transduction (cyclic AMP accumulation) assays. PGD2 and the highly selective DP‐specific agonist L‐644,698 ((4‐(3‐(3‐(3‐hydroxyoctyl)‐4‐oxo‐2‐thiazolidinyl) propyl) benzoic acid) (racemate)), but not PGE2 competed for [3H]‐PGD2‐specific binding to LS174T cell membranes (Ki values of 0.4 nM and 7 nM, respectively). The DP‐specific agonists PGD2, PGJ2, BW245C (5‐(6‐carboxyhexyl)‐1‐(3‐cyclohexyl‐3‐hydroxypropylhydantoin)), and L‐644,698 showed similar potencies in stimulating cyclic AMP accumulation (EC50 values: 45-90 nM) and demonstrated the expected rank order of potency. PGE2 also elicited cyclic AMP production in this cell line (EC50 value: 162 nM).The activation of cyclic AMP production by PGD2 and L‐644,698, but not PGE2, was inhibited by the selective DP antagonist BW A868C. Thus, PGD2 and L‐644,698 act through hDP in LS174T cells. PGD2, L‐644,698 and PGE2 (an established mucin secretagogue) potently stimulated mucin secretion in LS174T cells in a concentration‐dependent manner (EC50<50 nM). However, BW A868C effectively antagonized only the mucin secretion mediated by PGD2 and L‐644,698 and not PGE2. These data support a role for the DP receptor in the regulation of mucous secretion.British Journal of Pharmacology (2000) 131, 1537-1545; doi:10.1038/sj.bjp.0703688
참고문헌 (39)
BARRETT, KIM E..
Effect of Histamine and Other Mast Cell Mediators on T84 Epithelial Cellsa.
Annals of the New York Academy of Sciences,
vol.664,
no.1,
222-231.
Belley, Adam, Chadee, Kris.
Prostaglandin E2 stimulates rat and human colonic mucin exocytosis via the EP4 receptor.
Gastroenterology,
vol.117,
no.6,
1352-1362.
Belley, A, Keller, K, Grove, J, Chadee, K.
Interaction of LS174T human colon cancer cell mucins with Entamoeba histolytica: An in vitro model for colonic disease.
Gastroenterology,
vol.111,
no.6,
1484-1492.
Br. J. Pharmacol. BENNETT A. 357P 63 1978 The effects of prostaglandin D2 on the circular muscle of guinea‐pig isolated ileum and colon [proceedings]
BENNETT, A., PRATT, D., SANGER, G.J..
ANTAGONISM BY FENAMATES OF PROSTAGLANDIN ACTION IN GUINEA‐PIG AND HUMAN ALIMENTARY MUSCLE.
British journal of pharmacology : BJP,
vol.68,
no.3,
357-362.
Boie, Yves, Sawyer, Nicole, Slipetz, Deborah M., Metters, Kathleen M., Abramovitz, Mark.
Molecular Cloning and Characterization of the Human Prostanoid DP Receptor.
The Journal of biological chemistry,
vol.270,
no.32,
18910-18916.
Chadee, K, Petri Jr, W A, Innes, D J, Ravdin, J I.
Rat and human colonic mucins bind to and inhibit adherence lectin of Entamoeba histolytica..
The Journal of clinical investigation,
vol.80,
no.5,
1245-1254.
Pharmacol. Rev. COLEMAN R.A. 205 46 1994 International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes
Am. J. Physiol. FRIELING T. G132 266 1994 Effects of the inflammatory mediator prostaglandin D2 on submucosal neurons and secretion in guinea pig colon
Giles, H., Leff, P..
The biology and pharmacology of PGD2.
Prostaglandins,
vol.35,
no.2,
277-300.
Giles, Heather, Leff, P., Bolofo, Mary L., Kelly, M.G., Robertson, A.D..
The classification of prostaglandin DP‐receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist.
British journal of pharmacology : BJP,
vol.96,
no.2,
291-300.
Am. J. Physiol. GOERG K.J. G904 260 1991 Antisecretory effect of prostaglandin D2 in rat colon in vitro: action sites
Hirata, M, Kakizuka, A, Aizawa, M, Ushikubi, F, Narumiya, S.
Molecular characterization of a mouse prostaglandin D receptor and functional expression of the cloned gene..
Proceedings of the National Academy of Sciences of the United States of America,
vol.91,
no.23,
11192-11196.
J. Immunol. KAWATA R. 818 155 1995 10.4049/jimmunol.155.2.818 Prostaglandin synthase 1 and prostaglandin synthase 2 both participate in activation‐induced prostaglandin D2 production in mast cells
Lewis, R A, Soter, N A, Diamond, P T, Austen, K F, Oates, J A, Roberts 2nd, L J.
Prostaglandin D2 generation after activation of rat and human mast cells with anti-IgE..
The journal of immunology : official journal of the American Association of Immunologists,
vol.129,
no.4,
1627-1631.
Martínez, A, Miller, M J, Quinn, K, Unsworth, E J, Ebina, M, Cuttitta, F.
Non-radioactive localization of nucleic acids by direct in situ PCR and in situ RT-PCR in paraffin-embedded sections..
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society,
vol.43,
no.8,
739-747.
McCool, D J, Marcon, M A, Forstner, J F, Forstner, G G.
The T84 human colonic adenocarcinoma cell line produces mucin in culture and releases it in response to various secretagogues.
The Biochemical journal,
vol.267,
no.2,
491-500.
J. Immunol. MURAKAMI M. 4445 155 1995 10.4049/jimmunol.155.9.4445 IgE‐dependent activation of cytokine‐primed mouse cultured mast cells induces a delayed phase of prostaglandin D2 generation via prostaglandin endoperoxide synthase‐2
Oida, Hiroji, Hirata, Masakazu, Sugimoto, Yukihiko, Ushikubi, Fumitaka, Ohishi, Hitoshi, Mizuno, Noboru, Ichikawa, Atsushi, Narumiya, Shuh.
Expression of messenger RNA for the prostaglandin D receptor in the leptomeninges of the mouse brain.
FEBS letters,
vol.417,
no.1,
53-56.
Phillips, T.E., Stanley, C.M., Wilson, J..
The effect of 16,16-dimethyl prostaglandin E2 on proliferation of an intestinal goblet cell line and its synthesis and secretion of mucin glycoproteins.
Prostaglandins, leukotrienes, and essential fatty acids,
vol.48,
no.6,
423-428.
Plaisancié, Pascale, Bosshard, Arlette, Meslin, Jean-Claude, Cuber, Jean-Claude.
Colonic Mucin Discharge by a Cholinergic Agonist, Prostaglandins, and Peptide YY in the Isolated Vascularly Perfused Rat Colon.
Digestion,
vol.58,
no.2,
168-175.
Sanger, G.J., Jackson, A., Bennett, A..
A prostaglandin analogue which potently relaxes human uterus but not gut muscle.
European journal of pharmacology,
vol.81,
no.1,
141-143.
Seidler, U., Knafla, K., Kownatzki, R., Sewing, K-Fr..
Effects of endogenous and exogenous prostaglandins on glycoprotein synthesis and secretion in isolated rabbit gastric mucosa.
Gastroenterology,
vol.95,
no.4,
945-951.
Am. J. Physiol. SEIDLER U. G739 256 1989 Ca2+‐dependent and ‐independent secretagogue action on gastric mucus secretion in rabbit mucosal explants
Q. J. Microsc. Sci. STEEDMAN H.F. 477 91 1950 Alcian Blue 8GS: A new stain for mucin
Infect. Immun. TSE S.K. 1603 60 1992 10.1128/iai.60.4.1603-1612.1992 Biochemical characterization of rat colonic mucins secreted in response to Entamoeba histolytica
Urade, Y, Kitahama, K, Ohishi, H, Kaneko, T, Mizuno, N, Hayaishi, O.
Dominant expression of mRNA for prostaglandin D synthase in leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain..
Proceedings of the National Academy of Sciences of the United States of America,
vol.90,
no.19,
9070-9074.
Vanderheyden, P M L, Fierens, F L P, De Backer, J P, Fraeyman, N, Vauquelin, G.
Distinction between surmountable and insurmountable selective AT1 receptor antagonists by use of CHO‐K1 cells expressing human angiotensin II AT1 receptors.
British journal of pharmacology : BJP,
vol.126,
no.4,
1057-1065.
Whittle, B.J.R., Mugridge, K.G., Moncada, S..
Use of the rabbit transverse stomach-strip to identify and assay prostacyclin, PGA2, PGD2 and other prostaglandins.
European journal of pharmacology,
vol.53,
no.2,
167-172.
Hamish Wright, D., Metters, Kathleen M., Abramovitz, Mark, Ford‐Hutchinson, Anthony W..
Characterization of the recombinant human prostanoid DP receptor and identification of L‐644,698, a novel selective DP agonist.
British journal of pharmacology : BJP,
vol.123,
no.7,
1317-1324.
Wright, D.Hamish, Nantel, Francois, Metters, Kathleen M, Ford-Hutchinson, Anthony W.
A novel biological role for prostaglandin D2 is suggested by distribution studies of the rat DP prostanoid receptor.
European journal of pharmacology,
vol.377,
no.1,
101-115.
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