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Research Article Free access | 10.1172/JCI119677

Production and physiological actions of anandamide in the vasculature of the rat kidney.

D G Deutsch, M S Goligorsky, P C Schmid, R J Krebsbach, H H Schmid, S K Das, S K Dey, G Arreaza, C Thorup, G Stefano, and L C Moore

Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Department of Biochemistry & Cell Biology, State University of New York, Stony Brook, New York 11794, USA.

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Published September 15, 1997 - More info

Published in Volume 100, Issue 6 on September 15, 1997
J Clin Invest. 1997;100(6):1538–1546. https://doi.org/10.1172/JCI119677.
© 1997 The American Society for Clinical Investigation
Published September 15, 1997 - Version history
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Abstract

The endogenous cannabinoid receptor agonist anandamide is present in central and peripheral tissues. As the kidney contains both the amidase that degrades anandamide and transcripts for anandamide receptors, we characterized the molecular components of the anandamide signaling system and the vascular effects of exogenous anandamide in the kidney. We show that anandamide is present in kidney homogenates, cultured renal endothelial cells (EC), and mesangial cells; these cells also contain anandamide amidase. Reverse-transcriptase PCR shows that EC contain transcripts for cannabinoid type 1 (CB1) receptors, while mesangial cells have mRNA for both CB1 and CB2 receptors. EC exhibit specific, high-affinity binding of anandamide (Kd = 27.4 nM). Anandamide (1 microM) vasodilates juxtamedullary afferent arterioles perfused in vitro; the vasodilation can be blocked by nitric oxide (NO) synthase inhibition with L-NAME (0.1 mM) or CB1 receptor antagonism with SR 141716A (1 microM), but not by indomethacin (10 microM). Anandamide (10 nM) stimulates CB1-receptor-mediated NO release from perfused renal arterial segments; a similar effect was seen in EC. Finally, anandamide (1 microM) produces a NO-mediated inhibition of KCl-stimulated [3H]norepinephrine release from sympathetic nerves on isolated renal arterial segments. Hence, an anandamide signaling system is present in the kidney, where it exerts significant vasorelaxant and neuromodulatory effects.

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