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. PierceJ. W. Regan, R. A. Ross, M. F. Chan

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

1. Replacement of the carboxylic acid group of PGF(2α) with the non-acidic substituents hydroxyl (-OH) or methoxy (-OCH3) resulted in an unexpected activity profile. 2. Although PGF(2α) 1-OH and PGF(2α) 1-OCH3 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-OCH3 produced no Ca2+ 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-OCH3 did not attenuate Ca2+ 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-OCH3 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-OCH3, and classical FP receptor agonists. 5. Studies on smooth muscle preparations and cells containing DP, EP1, EP2, EP3, EP4, IP, and TP receptors indicated that the activity of PGF(2α) 1-OH and PGF(2α) 1-OCH3 could not be ascribed to interaction with these receptors. 6. The potent effects of PGF(2α) 1-OH and PGF(2α) 1-OCH3 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
DOIs
StatePublished - Jan 1 2000

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Keywords

  • 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., 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., ... 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. https://doi.org/10.1038/sj.bjp.0703462