Replacement of the carboxylic acid group of prostaglandin F(2α) with a hydroxyl or methoxy substituent provides biologically unique compounds

D. F. Woodward, A. H P Krauss, J. Chen, D. W. Gil, K. M. Kedzie, C. E. Protzman, L. Shi, R. Chen, H. A. Krauss, A. Bogardus, H. T T Dinh, L. A. Wheeler, S. W. Andrews, R. M. Burk, T. Gac, M. B. Roof, M. E. Garst, L. J. Kaplan, G. Sachs, K. L. Pierce & 3 others John W Regan, R. A. Ross, M. F. Chan

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

1. Replacement of the carboxylic acid group of PGF(2α) with the non-acidic substituents hydroxyl (-OH) or methoxy (-OCH 3) resulted in an unexpected activity profile. 2. Although PGF(2α) 1-OH and PGF(2α) 1-OCH 3 exhibited potent contractile effects similar to 17-phenyl PGF(2α) in the cat lung parenchymal preparation, they were approximately 1000 times less potent than 17-phenyl PGF(2α) in stimulating recombinant feline and human FP receptors. 3. In human dermal fibroblasts and Swiss 3T3 cells PGF(2α) 1-OH and PGF(2α) 1-OCH 3 produced no Ca 2+ signal until a 1 μM concentration was exceeded. Pretreatment of Swiss 3T3 cells with either 1 μM PGF(2α) 1-OH or PGF(2α) 1-OCH 3 did not attenuate Ca 2+ signal responses produced by PGF(2α) or fluprostenol. In the rat uterus, PGF(2α) 1-OH was about two orders of magnitude less potent than 17-phenyl PGF(2α) whereas PGF(2α) 1-OCH 3 produced only a minimal effect. 4. Radioligand binding studies on cat lung parenchymal plasma membrane preparations suggested that the cat lung parenchyma does not contain a homogeneous population of receptors that equally respond to PGF2(α)1-OH, PGF(2α)1-OCH 3, and classical FP receptor agonists. 5. Studies on smooth muscle preparations and cells containing DP, EP 1, EP 2, EP 3, EP 4, IP, and TP receptors indicated that the activity of PGF(2α) 1-OH and PGF(2α) 1-OCH 3 could not be ascribed to interaction with these receptors. 6. The potent effects of PGF(2α) 1-OH and PGF(2α) 1-OCH 3 on the cat lung parenchyma are difficult to describe in terms of interaction with the FP or any other known prostanoid receptor.

Original languageEnglish (US)
Pages (from-to)1933-1943
Number of pages11
JournalBritish Journal of Pharmacology
Volume130
Issue number8
StatePublished - 2000

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Prostaglandins F
Carboxylic Acids
Hydroxyl Radical
Cats
Swiss 3T3 Cells
Lung
Thromboxane Receptors
Dinoprost
Felidae

Keywords

  • Calcium (Ca )
  • FP receptor
  • Prostaglandin F(2α) (PGF(2α))
  • Prostanoids
  • Radioligad binding
  • Uterus

ASJC Scopus subject areas

  • Pharmacology

Cite this

Woodward, D. F., Krauss, A. H. P., Chen, J., Gil, D. W., Kedzie, K. M., Protzman, C. E., ... Chan, M. F. (2000). Replacement of the carboxylic acid group of prostaglandin F(2α) with a hydroxyl or methoxy substituent provides biologically unique compounds. British Journal of Pharmacology, 130(8), 1933-1943.

Replacement of the carboxylic acid group of prostaglandin F(2α) with a hydroxyl or methoxy substituent provides biologically unique compounds. / Woodward, D. F.; Krauss, A. H P; Chen, J.; Gil, D. W.; Kedzie, K. M.; Protzman, C. E.; Shi, L.; Chen, R.; Krauss, H. A.; Bogardus, A.; Dinh, H. T T; Wheeler, L. A.; Andrews, S. W.; Burk, R. M.; Gac, T.; Roof, M. B.; Garst, M. E.; Kaplan, L. J.; Sachs, G.; Pierce, K. L.; Regan, John W; Ross, R. A.; Chan, M. F.

In: British Journal of Pharmacology, Vol. 130, No. 8, 2000, p. 1933-1943.

Research output: Contribution to journalArticle

Woodward, DF, Krauss, AHP, Chen, J, Gil, DW, Kedzie, KM, Protzman, CE, Shi, L, Chen, R, Krauss, HA, Bogardus, A, Dinh, HTT, Wheeler, LA, Andrews, SW, Burk, RM, Gac, T, Roof, MB, Garst, ME, Kaplan, LJ, Sachs, G, Pierce, KL, Regan, JW, Ross, RA & Chan, MF 2000, 'Replacement of the carboxylic acid group of prostaglandin F(2α) with a hydroxyl or methoxy substituent provides biologically unique compounds', British Journal of Pharmacology, vol. 130, no. 8, pp. 1933-1943.
Woodward, D. F. ; Krauss, A. H P ; Chen, J. ; Gil, D. W. ; Kedzie, K. M. ; Protzman, C. E. ; Shi, L. ; Chen, R. ; Krauss, H. A. ; Bogardus, A. ; Dinh, H. T T ; Wheeler, L. A. ; Andrews, S. W. ; Burk, R. M. ; Gac, T. ; Roof, M. B. ; Garst, M. E. ; Kaplan, L. J. ; Sachs, G. ; Pierce, K. L. ; Regan, John W ; Ross, R. A. ; Chan, M. F. / Replacement of the carboxylic acid group of prostaglandin F(2α) with a hydroxyl or methoxy substituent provides biologically unique compounds. In: British Journal of Pharmacology. 2000 ; Vol. 130, No. 8. pp. 1933-1943.
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T1 - Replacement of the carboxylic acid group of prostaglandin F(2α) with a hydroxyl or methoxy substituent provides biologically unique compounds

AU - Woodward, D. F.

AU - Krauss, A. H P

AU - Chen, J.

AU - Gil, D. W.

AU - Kedzie, K. M.

AU - Protzman, C. E.

AU - Shi, L.

AU - Chen, R.

AU - Krauss, H. A.

AU - Bogardus, A.

AU - Dinh, H. T T

AU - Wheeler, L. A.

AU - Andrews, S. W.

AU - Burk, R. M.

AU - Gac, T.

AU - Roof, M. B.

AU - Garst, M. E.

AU - Kaplan, L. J.

AU - Sachs, G.

AU - Pierce, K. L.

AU - Regan, John W

AU - Ross, R. A.

AU - Chan, M. F.

PY - 2000

Y1 - 2000

N2 - 1. Replacement of the carboxylic acid group of PGF(2α) with the non-acidic substituents hydroxyl (-OH) or methoxy (-OCH 3) resulted in an unexpected activity profile. 2. Although PGF(2α) 1-OH and PGF(2α) 1-OCH 3 exhibited potent contractile effects similar to 17-phenyl PGF(2α) in the cat lung parenchymal preparation, they were approximately 1000 times less potent than 17-phenyl PGF(2α) in stimulating recombinant feline and human FP receptors. 3. In human dermal fibroblasts and Swiss 3T3 cells PGF(2α) 1-OH and PGF(2α) 1-OCH 3 produced no Ca 2+ signal until a 1 μM concentration was exceeded. Pretreatment of Swiss 3T3 cells with either 1 μM PGF(2α) 1-OH or PGF(2α) 1-OCH 3 did not attenuate Ca 2+ signal responses produced by PGF(2α) or fluprostenol. In the rat uterus, PGF(2α) 1-OH was about two orders of magnitude less potent than 17-phenyl PGF(2α) whereas PGF(2α) 1-OCH 3 produced only a minimal effect. 4. Radioligand binding studies on cat lung parenchymal plasma membrane preparations suggested that the cat lung parenchyma does not contain a homogeneous population of receptors that equally respond to PGF2(α)1-OH, PGF(2α)1-OCH 3, and classical FP receptor agonists. 5. Studies on smooth muscle preparations and cells containing DP, EP 1, EP 2, EP 3, EP 4, IP, and TP receptors indicated that the activity of PGF(2α) 1-OH and PGF(2α) 1-OCH 3 could not be ascribed to interaction with these receptors. 6. The potent effects of PGF(2α) 1-OH and PGF(2α) 1-OCH 3 on the cat lung parenchyma are difficult to describe in terms of interaction with the FP or any other known prostanoid receptor.

AB - 1. Replacement of the carboxylic acid group of PGF(2α) with the non-acidic substituents hydroxyl (-OH) or methoxy (-OCH 3) resulted in an unexpected activity profile. 2. Although PGF(2α) 1-OH and PGF(2α) 1-OCH 3 exhibited potent contractile effects similar to 17-phenyl PGF(2α) in the cat lung parenchymal preparation, they were approximately 1000 times less potent than 17-phenyl PGF(2α) in stimulating recombinant feline and human FP receptors. 3. In human dermal fibroblasts and Swiss 3T3 cells PGF(2α) 1-OH and PGF(2α) 1-OCH 3 produced no Ca 2+ signal until a 1 μM concentration was exceeded. Pretreatment of Swiss 3T3 cells with either 1 μM PGF(2α) 1-OH or PGF(2α) 1-OCH 3 did not attenuate Ca 2+ signal responses produced by PGF(2α) or fluprostenol. In the rat uterus, PGF(2α) 1-OH was about two orders of magnitude less potent than 17-phenyl PGF(2α) whereas PGF(2α) 1-OCH 3 produced only a minimal effect. 4. Radioligand binding studies on cat lung parenchymal plasma membrane preparations suggested that the cat lung parenchyma does not contain a homogeneous population of receptors that equally respond to PGF2(α)1-OH, PGF(2α)1-OCH 3, and classical FP receptor agonists. 5. Studies on smooth muscle preparations and cells containing DP, EP 1, EP 2, EP 3, EP 4, IP, and TP receptors indicated that the activity of PGF(2α) 1-OH and PGF(2α) 1-OCH 3 could not be ascribed to interaction with these receptors. 6. The potent effects of PGF(2α) 1-OH and PGF(2α) 1-OCH 3 on the cat lung parenchyma are difficult to describe in terms of interaction with the FP or any other known prostanoid receptor.

KW - Calcium (Ca )

KW - FP receptor

KW - Prostaglandin F(2α) (PGF(2α))

KW - Prostanoids

KW - Radioligad binding

KW - Uterus

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M3 - Article

VL - 130

SP - 1933

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JO - British Journal of Pharmacology

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