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Biomedical subjects

A Lucacchini

Publications and source records attributed to A Lucacchini.

189 records · Page 11Linked to original sources
PubMedDate not supplied

Characterization of a low affinity binding site for N6-substituted adenosine derivatives in rat testis membranes.

The binding characteristics of radiolabeled N6-(cyclohexyl)adenosine ([3H]CHA), N6-(R-phenylisopropyl)adenosine ([3H]R-PIA), 5'-N-ethyl-carboxamidoadenosine ([3H]NECA), and 2-[4-(2-carboxyethyl)phenyl]ethyl-amino-5'-N-ethylcarboxamidoadenosine ([3H]CGS 21680), to rat testis membranes were investigated. Specific binding of [3H]CGS 21680, a selective agonist for the A2a adenosine receptor, was very modest whilst the nonselective agonist [3H]NECA bound to rat testis membranes showing high binding capacity. At least two types of binding sites for [3H]NECA could be identified in rat testis membranes: high affinity sites and high capacity sites. Selective agonists for the A1 adenosine receptor, [3H]CHA and [3H]R-PIA bound with high affinity to a single class of binding sites. This high affinity binding site showed the typical pharmacological specificity of the A1 adenosine receptor with a potency order for agonists of CHA > or = R-PIA > NECA > N6-(S-phenylisopropyl)adenosine (S-PIA). In order to detect the presence of the A3 adenosine receptor in these membranes we selectively blocked the A1 receptor with a large molar excess of a xanthine antagonist, either 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) or xanthine amine congener (XAC). In the presence of an antagonist a low affinity binding site for [3H]CHA and [3H]R-PIA was detected. This low affinity binding site showed a different pharmacological specificity than the high affinity binding site. In fact the potency order for agonists was CHA > or = NECA = R-PIA > S-PIA. This finding suggests that the low affinity binding site represents the A3 adenosine receptor.

Adenosine↗
PubMedDate not supplied

Impaired glutathione reductase activity and levels of collagenase and elastase in synovial fluid in rheumatoid arthritis.

OBJECTIVE: To test the activity of elastase, collagenase and glutathione reductase in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and in patients with osteoarthritis (OA); to correlate the elastase and collagenase activity with the glutathione reductase activity, which is important for the inactivation of oxygen free radicals. METHODS: 24 patients affected by osteoarthrosis and 24 patients affected by rheumatoid arthritis took part in the study. We measured elastase activity towards the substrate metoxysuccinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide (MeOSuc-ala-ala-proval-p-NA) which is highly specific for elastase, and insensitive to the other serine proteases, such as cathepsin G; collagenase activity was measured using [14C]-acetylated collagen as the substrate. Glutathione reductase activity was measured following the oxidation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) in the presence of oxidized glutathione (GSSG). RESULTS: The concentrations of elastase, collagenase and glutathione reductase were statistically higher in patients with RA than in patients with OA. Moreover, in the SF of patients with RA we found positive correlation between enzyme activity levels. CONCLUSION: These results confirm a high activity of collagenase and elastase in the SF of patients with RA, which is about 30 times higher than that found in the SF of patients with OA. These data underline the synergic action of these enzymes in the pathogenesis of joint damage. RA patients also exhibit higher levels of glutathione reductase, which is important for the detoxification pathway of oxygen free radicals. However, compared with findings for collagenase and elastase, the increase in glutathione reductase is only three times higher than level found in the SF of OA patients. The limited increase in glutathione reductase activity during the inflammatory process might lead to an insufficient protective effect at the joint level in rheumatoid arthritis.

Adult↗
PubMedDate not supplied

A powerful inhibitor of guanine deaminase.

The synthesis of 9-(p-carbetoxyphenyl) guanine is reported. The assays carried out on guanine deaminase from rat and rabbit liver and pig brain show that this compound is a powerful inhibitor. The compound has a Ki = 5 micronM for the enzyme from pig brain. The use of the inhibitor for the synthesis of a specific adsorbent for guanine deaminase was studied.

Aminohydrolases↗
PubMedDate not supplied

Determination of adenosine kinase activity by high-pressure liquid chromatography.

High-pressure liquid chromatography (reverse-phase mode) was used to assay adenosine kinase in cell and tissue extracts. The method is optimized for a rapid and selective analysis using 6-methylthiopurine riboside as substrate, isocratic elution and detection at 300 nm. A complete separation of substrate and product is achieved in about 3 min with no interference by other UV-absorbing compounds; the limit of detection is 20 pmoles.

Adenosine Kinase↗
PubMedDate not supplied

Circular dichroism changes in adenosine deaminase upon substrate analog binding.

Circular dichroism studies with adenosine deaminase from calf intestinal mucosa are described. Addition of purine riboside, a competitive inhibitor of the enzyme, does not cause modification of mean residue ellipticity in the CD spectra in the region between 250 and 185 nm, but increases markedly the ellipticity in the 300-250 nm region. The data are consistent with the view that a conformational change involving aromatic amino acid residues occurs upon binding of purine riboside to adenosine binding site of adenosine deaminase.

Adenosine Deaminase↗
PubMedDate not supplied

1,2,3-Triazolo [4,5-d] pyridazines--V. Preparation and adenosine receptor binding of new 4-amino derivatives.

This paper reports the continuation of studies on the 4-aminosubstituted 1,2,3-triazolo [4,5-d] pyridazine derivatives which had shown binding affinity towards A1-adenosine receptors. 1-Benzyl derivatives bearing new amines and new 1-(substituted benzyl) derivatives were prepared and tested. The biological results showed that some compounds possessed high affinity (approximately 30-70 nM) and good selectivity toward the A1-adenosine receptors. Further information about structure-biological activity relationships was aquired.

Animals↗
PubMedDate not supplied

Isosteric replacement of amide by ester function. Synthesis and benzodiazepine receptor affinity of indol-3-ylglyoxylyl ester derivatives.

A number of benzyl and phenylethyl esters of indol-3-ylglyoxylic acid were synthesized and tested for their ability to displace [3H]Ro 15-1788 binding from bovine brain membranes. In these new compounds the oxygen atom of the ester function replaced the amide NH group of a class of previously described indolylglyoxylylamides, since it is reported in literature that in the beta-carboline series an ester function is more favourable to the activity than an amide group. However, none of the compounds showed an affinity at the Benzodiazepine receptor higher than that of the corresponding amides, demonstrating that the presence of the amide NH group is favourable to the interaction of ligands with the receptor site.

Amides↗