L-Canavanine sulfate

Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid.[Pubmed:7071589]

Science. 1982 Apr 23;216(4544):415-7.

Hematologic and serologic abnormalities similar to those observed in human systemic lupus erythematosus (SLE) developed in cynomolgus macaques fed alfalfa sprouts. L-Canavanine sulfate, a constituent of alfalfa sprouts, was incorporated into the diet and reactivated the syndrome in monkeys in which an SLE-like syndrome had previously been induced by the ingestion of alfalfa seeds or sprouts.

Selective inhibitors of neuronal nitric oxide synthase--is no NOS really good NOS for the nervous system?[Pubmed:9226999]

Trends Pharmacol Sci. 1997 Jun;18(6):204-11.

It is now ten years since NO was shown to account for the biological activity of endothelium-derived relaxing factor (EDRF). It is also the tenth anniversary of the identification of L-NG monomethyl arginine (L-NMMA) as the very first inhibitor of NO biosynthesis. That EDRF and NO were one and the same sparked an explosion of interest in the biochemistry and pharmacology of NO which has yet to subside. In contrast, the first ever nitric oxide synthase (NOS) inhibitor slipped seamlessly into the literature virtually without comment at the time. Over the following decade, L-NMMA (and like NOS inhibitors) have proved invaluable as tools for probing the biological roles of NO in health and disease and, in particular, have increased our understanding of the function of NO in the nervous system. Further advances in this important area now require the development of inhibitors selective for the neuronal isoform of NOS (nNOS). Here, Philip Moore and Rachel Handy provide an up-to-date account of the literature regarding the biochemical and pharmacological characterization of NOS inhibitors with particular reference to compounds with greater selectivity for the nNOS isoform.

Facilitatory effects of somatostatin on reduced uptake of 2-deoxyglucose in cerebral cortical and hippocampal slices from aged rats.[Pubmed:7851504]

Eur J Pharmacol. 1994 Oct 14;269(2):269-72.

The aim of the present study was to determine whether or not the reduction of 2-deoxyglucose uptake by the cerebral cortical slices in aged rats (22-23 months old) was attenuated by somatostatin or carbachol. In 8-week-old rats, somatostatin and carbachol produced concentration-dependent increases in 2-deoxyglucose uptake. 2-Deoxyglucose uptake of the cortical slices in 22-23-month-old rats was significantly facilitated by treatment with 0.1-1 microM somatostatin or 1-100 microM carbachol. Metabolic responses to somatostatin or carbachol were quite similar in young and aged rats. The present results demonstrated that 2-deoxyglucose uptake by the cerebral cortex was facilitated by somatostatin and carbachol in both young and old rats.

L-canavanine restores blood pressure in a rat model of endotoxic shock.[Pubmed:7535234]

Eur J Pharmacol. 1994 Dec 12;271(1):87-92.

Administration of lipopolysaccharide to anaesthetised rats produced a reduction in mean arterial pressure, an increase in heart rate, and death at 4-6 h. Intravenous infusion of NG-nitro-L-arginine methyl ester (50 mg/kg), an inhibitor of constitutive and inducible nitric oxide (NO) synthase, 60 min after challenge with lipopolysaccharide, caused an immediate increase in blood pressure followed by a precipitous fall in pressure, and death. In contrast, intravenous infusion of L-canavanine (100 mg/kg), reported to be a selective inhibitor of inducible NO synthase in vitro, 60 min and 180 min after lipopolysaccharide challenge, produced an increase in mean arterial pressure and reversed the lipopolysaccharide induced hypotension. However, in lipopolysaccharide challenged animals protected from hypotension by administration of L-canavanine (60 min post challenge), intravenous infusion of NG-nitro-L-arginine methyl ester at 180 min post challenge caused an immediate rise in mean arterial pressure, followed by a rapid fall in blood pressure and heart rate, and sudden death. In contrast, a second dose of L-canavanine at 180 min post challenge maintained blood pressure for the duration of the experiment. These findings indicate that inhibition of both constitutive and inducible NO synthase during endotoxaemia is lethal. However, the use of a selective inhibitor of inducible NO synthase restores mean arterial pressure to baseline, and offers a therapeutic approach to managing hypotension in shock.