Abstract
The dibasic amino acid, l-arginine, is a substrate for both nitric oxide synthase (NOS) and arginase and therefore, plays an important role in cell signaling and cell growth. We examined the effects of various NOS inhibitors on l-arginine transport into rat renal brush border membrane (BBM) vesicles.l-Arginine uptake was stimulated in the presence of an inwardly directed Na+ gradient and an imposed inside negative potential in BBM but not basolateral membrane vesicles. In BBM vesicles, the l-arginine analogs, N-iminoethyl-l-orinithine and Nw-monomethyl-l-arginine (L-NMMA) were potent inhibitors of l-arginine uptake (IC50 of 0.48 and 0.82 mM, respectively), while Nw-nitro-l-arginine was less active (IC50 = 10 mM) and Nw-nitro-l-arginine methyl ester (L-NAME) was inactive. The inhibition of l-arginine transport by L-NMMA was competitive in nature. L-NIO, L-NMMA as well asl-arginine and l-lysine but not Nw-nitro-l-arginine methyl ester, trans-stimulated l-arginine uptake when preloaded into BBM vesicles. The l-arginine analogs had no effect on the transport of the neutral amino acid, l-leucine, in the same preparations. The data suggest that in addition to inhibiting NOS, thel-arginine analogs, N-iminoethyl-l-orinithine, L-NMMA and to a lesser extent L-NA, also inhibit l-arginine transport across the BBM of proximal tubules.
Footnotes
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Send reprint requests to: Dr. Richard Edwards, SmithKline Beecham, Department of Renal Pharmacology, W2521, 709 Swedeland Road, P.O. Box 1539, King of Prussia, PA 19406-0939.
- Abbreviations:
- NOS
- nitric oxide synthase
- NO
- nitric oxide
- BBM
- brush border membrane
- BLM
- basolateral membrane
- L-NIO
- N-iminoethyl-l-orininthine
- L-NMMA
- Nw-monomethyl-l-arginine
- L-NA
- Nw-nitro-l-arginine
- L-NAME
- Nw-nitro-l-arginine methyl ester
- HEPES
- N-[2-hydroxyethyl] piperazine-N′-[2-ethanesulfonic acid]
- Tris
- Tris[hydoxymethyl]aminomethane.
- Received September 29, 1997.
- Accepted January 23, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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