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Production and actions of the anandamide metabolite prostamide E2 in the renal medulla.
J Pharmacol Exp Ther. 2012 Sep; 342(3):770-9.JP

Abstract

Medullipin has been proposed to be an antihypertensive lipid hormone released from the renal medulla in response to increased arterial pressure and renal medullary blood flow. Because anandamide (AEA) possesses characteristics of this purported hormone, the present study tested the hypothesis that AEA or one of its metabolites represents medullipin. AEA was demonstrated to be enriched in the kidney medulla compared with cortex. Western blotting and enzymatic analyses of renal cortical and medullary microsomes revealed opposite patterns of enrichment of two AEA-metabolizing enzymes, with fatty acid amide hydrolase higher in the renal cortex and cyclooxygenase-2 (COX-2) higher in the renal medulla. In COX-2 reactions with renal medullary microsomes, prostamide E2, the ethanolamide of prostaglandin E₂, was the major product detected. Intramedullarily infused AEA dose-dependently increased urine volume and sodium and potassium excretion (15-60 nmol/kg/min) but had little effect on mean arterial pressure (MAP). The renal excretory effects of AEA were blocked by intravenous infusion of celecoxib (0.1 μg/kg/min), a selective COX-2 inhibitor, suggesting the involvement of a prostamide intermediate. Plasma kinetic analysis revealed longer elimination half-lives for AEA and prostamide E2 compared with prostaglandin E₂. Intravenous prostamide E2 reduced MAP and increased renal blood flow (RBF), actions opposite to those of angiotensin II. Coinfusion of prostamide E2 inhibited angiotensin II effects on MAP and RBF. These results suggest that AEA and/or its prostamide metabolites in the renal medulla may represent medullipin and function as a regulator of body fluid and MAP.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, 1217 E. Marshall St., Medical Sciences Bldg., Room 531, Richmond, VA 23298-0613, USA. jkritter@vcu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22685343

Citation

Ritter, Joseph K., et al. "Production and Actions of the Anandamide Metabolite Prostamide E2 in the Renal Medulla." The Journal of Pharmacology and Experimental Therapeutics, vol. 342, no. 3, 2012, pp. 770-9.
Ritter JK, Li C, Xia M, et al. Production and actions of the anandamide metabolite prostamide E2 in the renal medulla. J Pharmacol Exp Ther. 2012;342(3):770-9.
Ritter, J. K., Li, C., Xia, M., Poklis, J. L., Lichtman, A. H., Abdullah, R. A., Dewey, W. L., & Li, P. L. (2012). Production and actions of the anandamide metabolite prostamide E2 in the renal medulla. The Journal of Pharmacology and Experimental Therapeutics, 342(3), 770-9. https://doi.org/10.1124/jpet.112.196451
Ritter JK, et al. Production and Actions of the Anandamide Metabolite Prostamide E2 in the Renal Medulla. J Pharmacol Exp Ther. 2012;342(3):770-9. PubMed PMID: 22685343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Production and actions of the anandamide metabolite prostamide E2 in the renal medulla. AU - Ritter,Joseph K, AU - Li,Cao, AU - Xia,Min, AU - Poklis,Justin L, AU - Lichtman,Aron H, AU - Abdullah,Rehab A, AU - Dewey,William L, AU - Li,Pin-Lan, Y1 - 2012/06/08/ PY - 2012/6/12/entrez PY - 2012/6/12/pubmed PY - 2013/3/8/medline SP - 770 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 342 IS - 3 N2 - Medullipin has been proposed to be an antihypertensive lipid hormone released from the renal medulla in response to increased arterial pressure and renal medullary blood flow. Because anandamide (AEA) possesses characteristics of this purported hormone, the present study tested the hypothesis that AEA or one of its metabolites represents medullipin. AEA was demonstrated to be enriched in the kidney medulla compared with cortex. Western blotting and enzymatic analyses of renal cortical and medullary microsomes revealed opposite patterns of enrichment of two AEA-metabolizing enzymes, with fatty acid amide hydrolase higher in the renal cortex and cyclooxygenase-2 (COX-2) higher in the renal medulla. In COX-2 reactions with renal medullary microsomes, prostamide E2, the ethanolamide of prostaglandin E₂, was the major product detected. Intramedullarily infused AEA dose-dependently increased urine volume and sodium and potassium excretion (15-60 nmol/kg/min) but had little effect on mean arterial pressure (MAP). The renal excretory effects of AEA were blocked by intravenous infusion of celecoxib (0.1 μg/kg/min), a selective COX-2 inhibitor, suggesting the involvement of a prostamide intermediate. Plasma kinetic analysis revealed longer elimination half-lives for AEA and prostamide E2 compared with prostaglandin E₂. Intravenous prostamide E2 reduced MAP and increased renal blood flow (RBF), actions opposite to those of angiotensin II. Coinfusion of prostamide E2 inhibited angiotensin II effects on MAP and RBF. These results suggest that AEA and/or its prostamide metabolites in the renal medulla may represent medullipin and function as a regulator of body fluid and MAP. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/22685343/Production_and_actions_of_the_anandamide_metabolite_prostamide_E2_in_the_renal_medulla_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=22685343 DB - PRIME DP - Unbound Medicine ER -