Influence of agmatine in adaptation of cAMP signal transduction system of opiate receptors.
(9/193)
AIM: To observe attenuative effects of agmatine on opiate desensitization and substance dependence. METHODS: Guanosine 5'-O-(3-[35S] thiotriphosphate) ([35S]GTTP) binding and cellular cyclic AMP (cAMP) level were determined by radioligand binding assay and radioimmunoassay in NG108-15 cells, respectively. RESULTS: Agmatine increased stimulative action of opioids on [35S]GTTP binding by about 35% and inhibitory effects of opioids on cellular cAMP concentration by about 114.3% in NG108-15 cells pretreated with opioids. On the other hand, it also inhibited cAMP over-shooting by 214.9% of morphine substance dependent cells precipitated by naloxone compared with that of control. These effects of agmatine were antagonized by idazoxan in a concentration-dependent manner. CONCLUSION: Agmatine reversed the formative process of adaptation in cAMP signal transduction cascade. (+info)
Dual interaction of agmatine with the rat alpha(2D)-adrenoceptor: competitive antagonism and allosteric activation.
(10/193)
In segments of rat vena cava preincubated with [(3)H]-noradrenaline and superfused with physiological salt solution, the influence of agmatine on the electrically evoked [(3)H]-noradrenaline release, the EP(3) prostaglandin receptor-mediated and the alpha(2D)-adrenoceptor-mediated inhibition of evoked [(3)H]-noradrenaline release was investigated. Agmatine (0.1-10 microM) by itself was without effect on evoked [(3)H]-noradrenaline release. In the presence of 10 microM agmatine, the prostaglandin E(2)(PGE(2))-induced EP(3)-receptor-mediated inhibition of [(3)H]-noradrenaline release was not modified, whereas the alpha(2D)-adrenoceptor-mediated inhibition of [(3)H]-noradrenaline release induced by noradrenaline, moxonidine or clonidine was more pronounced than in the absence of agmatine. However, 1 mM agmatine antagonized the moxonidine-induced inhibition of [(3)H]-noradrenaline release. Agmatine concentration-dependently inhibited the binding of [(3)H]-clonidine and [(3)H]-rauwolscine to rat brain cortex membranes (K(i) values 6 microM and 12 microM, respectively). In addition, 30 and 100 microM agmatine increased the rate of association and decreased the rate of dissociation of [(3)H]-clonidine resulting in an increased affinity of the radioligand for the alpha(2D)-adrenoceptors. [(14)C]-agmatine labelled specific binding sites on rat brain cortex membranes. In competition experiments. [(14)C]-agmatine was inhibited from binding to its specific recognition sites by unlabelled agmatine, but not by rauwolscine and moxonidine. In conclusion, the present data indicate that agmatine both acts as an antagonist at the ligand recognition site of the alpha(2D)-adrenoceptor and enhances the effects of alpha(2)-adrenoceptor agonists probably by binding to an allosteric binding site of the alpha(2D)-adrenoceptor which seems to be labelled by [(14)C]-agmatine. (+info)
Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.
(11/193)
Antagonists of glutamate receptors of the N-methyl-d-aspartate subclass (NMDAR) or inhibitors of nitric oxide synthase (NOS) prevent nervous system plasticity. Inflammatory and neuropathic pain rely on plasticity, presenting a clinical opportunity for the use of NMDAR antagonists and NOS inhibitors in chronic pain. Agmatine (AG), an endogenous neuromodulator present in brain and spinal cord, has both NMDAR antagonist and NOS inhibitor activities. We report here that AG, exogenously administered to rodents, decreased hyperalgesia accompanying inflammation, normalized the mechanical hypersensitivity (allodynia/hyperalgesia) produced by chemical or mechanical nerve injury, and reduced autotomy-like behavior and lesion size after excitotoxic spinal cord injury. AG produced these effects in the absence of antinociceptive effects in acute pain tests. Endogenous AG also was detected in rodent lumbosacral spinal cord in concentrations similar to those previously detected in brain. The evidence suggests a unique antiplasticity and neuroprotective role for AG in processes underlying persistent pain and neuronal injury. (+info)
Antifungal compound, feruloylagmatine, induced in winter wheat exposed to a low temperature.
(12/193)
An antifungal compound, feruloylagmatine [1-(trans -4'-hydroxy-3'- methoxycinnamoylamino)-4-guanidinobutanel, was isolated from crowns of winter wheat (Triticum aestivum L. cv Chihokukomugi). Its structure was identified by NMR, MS and UV spectral analyses. It was also confirmed by an HPLC analysis that the compound was induced in wheat by a low temperature. (+info)
Interaction between arginase and L-ornithine carbamoyltransferase in Saccharomyces cerevisiae. The regulatory sites of arginase.
(13/193)
The inhibition of ornithine carbamoyltransferase by arginase in Saccharomyces cerevisiae, which is under the control or arginine and ornithine, involves a regulatory site for arginine on the arginase distinct from its catalytic site. This regulatory site is responsible for the reinforcement effect of arginine on the inhibition of ornithine carbamoyltransferase by arginase. The binding site of ornithine carbamoyltransferase on arginase is also shown by our analysis. (+info)
Isolation, characterization, and mapping of Escherichia coli mutants blocked in the synthesis of ornithine decarboxylase.
(14/193)
Several Escherichia coli K-12 mutants blocked in the synthesis of ornithine decarboxylase (OD) were isolated after transduction for serA+ in a strain (MA197) blocked in agmatine ureohydrolase (AUH) with a mutagenized phage lysate of P1. The new double-polyamine mutants were characterized by an unconditional polyamine dependence; either putrescine or spermidine was required for normal growth. The mutational block was varified by the demonstration of a virtual absence of OD activity in cellular extracts. The mutation, designated speC, was mapped by P1 transduction in several strains and was shown to have a cotransduction frequency of 17.2% with serA. Map order was established as serA speB speC metK. A derivative of one of the OD mutants having wild-type levels of AUH and blocked in OD was utilized along with an OD AUH mutant and an OD+ AUH strain to explore the phenomenon of "pathway selection" using growth rate as a parameter. Polyamine pool studies were carried out simultaneously. The results presented here support the hypothesis of pathway selection, implying a preferential utilization of exogenous arginine rather than endogenously produced arginine in polyamine biosynthesis. (+info)
Positive inotropic effects of imidazoline derivatives are not mediated via imidazoline binding sites but alpha1-adrenergic receptors.
(15/193)
Imidazoline-binding sites are non-adrenergic receptors and classified into I11/I2 subtypes. There is strong evidence that I1-binding sites, located in the rostro-ventrolateral medulla, are involved in regulation of blood pressure. However, less is known about the peripheral participation of I1-binding sites in cardiovascular reactions. Therefore, the aim of this study was to investigate whether specific imidazoline derivatives influence myocardial contractility and whether imidazoline binding sites are expressed in rat heart. Agmatine, clonidine and idazoxan failed to alter inotropy in left atria within the whole concentration range tested (1 nM - 100 microM), whereas cirazoline (1- 100 microM) and moxonidine (100 microM) increase inotropy by about 20-30%. After preincubation with the alpha1-adrenoceptor antagonist prazosin, the cirazoline and moxonidine stimulated inotropy was antagonized, indicating more an alpha1-adrenergic and less an imidazoline binding site mediated mechanism. Radioligand-binding studies in membranes of left ventricles using [3H]-clonidine to specify I1-binding yielded KD values of 12.7 microM, confirming the functional results of an absence of I1-binding sites in ventricles of rats. However, the existence of low affinity I2-binding sites determined by [3H]-idazoxan labeling could not be excluded since a KD of 0.5 microM was calculated and since competition studies with guanabenz (Ki = 0.1 microM), clonidine (Ki = 58.1 microM) and moxonidine (Ki = 129 microM) confirmed the specificity of the I2-binding. (+info)
Agmatine inhibits cell proliferation and improves renal function in anti-thy-1 glomerulonephritis.
(16/193)
Changes in the expression of alternate arginine metabolic pathways have been implicated in the pathogenesis of experimental glomerulonephritis. Agmatine, decarboxylated arginine, has been shown in vitro to suppress both inducible nitric oxide synthase and the rate-limiting enzyme of polyamine biosynthesis, ornithine decarboxylase (ODC). This study was undertaken to determine whether agmatine administration could reduce tissue injury by decreasing nitric oxide, and reduce cell proliferation, by diminishing ODC activity, in experimental mesangial proliferative glomerulonephritis (Thy-1 nephritis). Agmatine treatment (50 mg/kg per d intraperitoneally) in Thy-1 nephritis rats prevented a reduction in GFR at day 1. Agmatine treatment decreased nitric oxide production in Thy-1 nephritis rats by 23% and 41% at days 1 and 4, respectively. Agmatine treatment also reduced ODC activity and glomerular (3)H-thymidine incorporation on days 1, 4, and 7. Histologic evaluation revealed a decline in mesangial cell proliferation and extracellular matrix accumulation associated with agmatine treatment administered before or 24 h after Thy-1 antibody, and this was confirmed by a reduction in the number of cells expressing proliferating cell nuclear antigen on days 4 and 7. These studies provide the first in vivo evidence that agmatine administration can reduce cellular proliferation in Thy-1 nephritis and attenuate the initial reduction in renal function associated with this model. (+info)