Prostaglandin Ethanolamides (Prostamides): In Vitro Pharmacology and Metabolism

I. Matias, J. Chen, L. De Petrocellis, T. Bisogno, A. Ligresti, F. Fezza, A. H P Krauss, L. Shi, C. E. Protzman, C. Li, Y. Liang, A. L. Nieves, K. M. Kedzie, R. M. Burk, V. Di Marzo, D. F. Woodward

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Abstract

We investigated whether prostaglandin ethanolamides (prostamides) E 2, F, and D2 exert some of their effects by 1) activating prostanoid receptors either per se or after conversion into the corresponding prostaglandins; 2) interacting with proteins for the inactivation of the endocannabinoid N-arachidonoylethanolamide (AEA), for example fatty acid amide hydrolase (FAAH), thereby enhancing AEA endogenous levels; or 3) activating the vanilloid receptor type-1 (TRPV1). Prostamides potently stimulated cat iris contraction with potency approaching that of the corresponding prostaglandins. However, prostamides D2, E 2, and F exhibited no meaningful interaction with the cat recombinant FP receptor, nor with human recombinant DP, EP 1-4, FP, IP, and TP prostanoid receptors. Prostamide F was also very weak or inactive in a panel of bioassays specific for the various prostanoid receptors. None of the prostamides inhibited AEA enzymatic hydrolysis by FAAH in cell homogenates, or AEA cellular uptake in intact cells. Furthermore, less than 3% of the compounds were hydrolyzed to the corresponding prostaglandins when incubated for 4 h with homogenates of rat brain, lung, or liver, and cat iris or ciliary body. Very little temperature-dependent uptake of prostamides was observed after incubation with rat brain synaptosomes or RBL-2H3 cells. We suggest that prostamides' most prominent pharmacological actions are not due to transformation into prostaglandins, activation of prostanoid receptors, enhancement of AEA levels, or gating of TRPV1 receptors, but possibly to interaction with novel receptors that seem to be functional in the cat iris.

Original languageEnglish
Pages (from-to)745-757
Number of pages13
JournalJournal of Pharmacology and Experimental Therapeutics
Volume309
Issue number2
DOIs
Publication statusPublished - May 2004

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Prostaglandins
Pharmacology
Cats
Iris
In Vitro Techniques
Thromboxane Receptors
Endocannabinoids
Ciliary Body
Synaptosomes
Brain
Biological Assay
Hydrolysis
anandamide
Lung
Temperature
Liver

ASJC Scopus subject areas

  • Pharmacology

Cite this

Matias, I., Chen, J., De Petrocellis, L., Bisogno, T., Ligresti, A., Fezza, F., ... Woodward, D. F. (2004). Prostaglandin Ethanolamides (Prostamides): In Vitro Pharmacology and Metabolism. Journal of Pharmacology and Experimental Therapeutics, 309(2), 745-757. https://doi.org/10.1124/jpet.103.061705

Prostaglandin Ethanolamides (Prostamides) : In Vitro Pharmacology and Metabolism. / Matias, I.; Chen, J.; De Petrocellis, L.; Bisogno, T.; Ligresti, A.; Fezza, F.; Krauss, A. H P; Shi, L.; Protzman, C. E.; Li, C.; Liang, Y.; Nieves, A. L.; Kedzie, K. M.; Burk, R. M.; Di Marzo, V.; Woodward, D. F.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 309, No. 2, 05.2004, p. 745-757.

Research output: Contribution to journalArticle

Matias, I, Chen, J, De Petrocellis, L, Bisogno, T, Ligresti, A, Fezza, F, Krauss, AHP, Shi, L, Protzman, CE, Li, C, Liang, Y, Nieves, AL, Kedzie, KM, Burk, RM, Di Marzo, V & Woodward, DF 2004, 'Prostaglandin Ethanolamides (Prostamides): In Vitro Pharmacology and Metabolism', Journal of Pharmacology and Experimental Therapeutics, vol. 309, no. 2, pp. 745-757. https://doi.org/10.1124/jpet.103.061705
Matias, I. ; Chen, J. ; De Petrocellis, L. ; Bisogno, T. ; Ligresti, A. ; Fezza, F. ; Krauss, A. H P ; Shi, L. ; Protzman, C. E. ; Li, C. ; Liang, Y. ; Nieves, A. L. ; Kedzie, K. M. ; Burk, R. M. ; Di Marzo, V. ; Woodward, D. F. / Prostaglandin Ethanolamides (Prostamides) : In Vitro Pharmacology and Metabolism. In: Journal of Pharmacology and Experimental Therapeutics. 2004 ; Vol. 309, No. 2. pp. 745-757.
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