Implication of glucocorticoid in anti-inflammatory effects of Ro5-4864 in mouse pleurisy induced by carrageenan.

Mouse pleurisy induced by carrageenan is used to determine the mechanism of anti-inflammatory action of 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiazepin-2 (Ro5-4864). Pre-treatment with Ro5-4864 inhibits different inflammatory parameters, such as neutrophil influx, MPO activity and NO levels in the early phase (4 h), as well as mononuclear cells and ADA activity in the late phase (48 h) of pleurisy. dl-Aminoglutethimide, inhibitor of steroidal synthesis, reverted the effect of Ro5-4864 on these different inflammatory parameters.

Involvement of steroids in anti-inflammatory effects of PK11195 in a murine model of pleurisy.

Background: Studies on peripheral benzodiazepine receptor function have yielded a diverse list of activities of which the anti-inflammatory effects need to be further examined.

Aims: To evaluate the role of steroids, nitric oxide and adenosine-deaminase in the anti-inflammatory effect of PK11195.

Methods: Pleurisy was induced by intrapleural injection of carrageenan in mice pre-treated or not with PK11195.

Antinociceptive effects of peripheral benzodiazepine receptors.

Pretreatment of mice with Ro5-4864 or PK11195 inhibited the first- and second-phase responses in the formalin test and this effect was significantly reversed by aminoglutethimide, an inhibitor of pregnenolone synthesis, suggesting that the antinociceptive effect of the peripheral-type benzodiazepine receptor ligands is dependent on steroid formation. Doses of Ro5-4864 that did not produce an antinociceptive effect when injected by the intraperitoneal route presented an analgesic effect, if infected by the intracerebroventricular, intrathecal or intraplantar routes. PK11195 pretreatments with intrathecal, intracerebroventricular or intraplantar doses had no effect in the formalin test.

Involvement of steroids in anti-inflammatory effects of peripheral benzodiazepine receptor ligands.

Mouse paw oedema induced by carrageenan is used to determine if glucocorticoids are involved in the anti-inflammatory effects of peripheral benzodiazepine receptor ligands. The anti-inflammatory responses elicited by i.p.

Antidepressant-like effect of Ro5-4864, a peripheral-type benzodiazepine receptor ligand, in forced swimming test.

This study examined the effects of peripheral-type benzodiazepine receptors in the forced swimming test. PK 11195 (1-(2-chloro-phenyl)-N-methyl-N-(1-methylpropyl)-1-isoquinoline carboxamide) and Ro5-4864 (7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepine-2-one) were i.p.

Comparison of two PBR ligands with classical antiinflammatory drugs in LPS-induced arthritis in rats.

The antinociceptive and anti-edematogenic effects of peripheral benzodiazepine receptor (PBR) ligands, Ro5-4864 (7-chloro-5- (4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiazepine-2) and PK11195 (1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide), were studied in an experimental model of carrageenan/LPS -induced arthritis in rats. These effects were compared with those of indomethacin and dexamethasone. Both pre and post-treatments with PK11195 were found to be anti-edematogenic and antinociceptive.

Effects of central and systemic injections of peripheral benzodiazepine receptor ligands on the anxiolytic actions of ethanol in rats.

The influence of peripheral benzodiazepine receptor ligands Ro5-4864 (0.05 or 1.0 mg/kg, i.

Anti-inflammatory effects of peripheral benzodiazepine receptor ligands in two mouse models of inflammation.

In vivo treatment of mice with peripheral benzodiazepine receptor ligands exerts an inhibitory effect on the inflammatory response in two models of acute inflammation. In the first model, pretreatment of the animals (24 h) with 1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) and 7-chloro-5-(4-Chlorophenyl)-1, 3-dihydro-1-methyl-2-H-1,4-benzodiazepin-2 (Ro5-4864), at different doses (0.00001-10 mg/kg, i.

Potential role of peripheral benzodiazepine receptors in inflammatory responses.

This study investigates the anti-inflammatory effects of 1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide and 7-chloro-5-(4-chlorophenyl)-1, 3-dihydro-1-methyl-2-H-1,4-benzodiazepin-2-one in paw oedema induced by carrageenan in mice. Pretreatment (24 h) with both ligands inhibited oedema formation in at different doses (0.00001-10 mg/kg, i.

The Mr 18,000 subunit of the peripheral-type benzodiazepine receptor exhibits both benzodiazepine and isoquinoline carboxamide binding sites in the absence of the voltage-dependent anion channel or of the adenine nucleotide carrier.

The peripheral type benzodiazepine receptor (PBR) binds benzodiazepines such as RO5-4864 and isoquinoline carboxamide derivatives such as PK11195. This receptor includes an Mr 18,000 isoquinoline-binding subunit predominantly located in mitochondrial mem- branes. This protein has been found to copurify with two other mitochondrial proteins, namely the outer membrane voltage-dependent anion channel (VDAC), also known as mitochondrial porin, and the inner membrane adenine nucleotide carrier.

High-level production of a human membrane protein in yeast: the peripheral-type benzodiazepine receptor.

The human peripheral-type benzodiazepine receptor (PBR) has been produced in Saccharomyces cerevisiae where it retains its pharmacological properties [Riond et al., Eur. J.

Site-directed mutagenesis of the peripheral benzodiazepine receptor: identification of amino acids implicated in the binding site of Ro5-4864.

The peripheral benzodiazepine receptor (PBR) is an 18-kDa protein present in the outer mitochondrial membrane. The human PBR can be labeled with the benzodiazepine Ro5-4864 and with the isoquinoline carboxamide PK11195. The two ligands compete with each other in binding experiments, with previous results suggesting overlapping but not identical binding sites.

Effects of morphine withdrawal syndrome on endo-oligopeptidase (EC 3.4.22.19) activity.

Endo-oligopeptidase (EC 3.4.22.

Molecular basis for the different binding properties of benzodiazepines to human and bovine peripheral-type benzodiazepine receptors.

The 18 kDa peripheral benzodiazepine receptor (PBR) can be labelled by benzodiazepines, such as Ro5-4864, and isoquinoline carboxamides such as PK11195. These two compounds are reversible competitive inhibitors of each other. However, while the binding affinity of Ro5-4864 varies enormously across species, PK11195 always displays high affinity, suggesting that their binding domains are overlapping but not identical.

Opioid receptor types in the brain of the Afghan pika (Ochotona rufescens), a species which is naturally tolerant to morphine.

The rabbit is normally sensitive to morphine while another lagomorph, the Afghan pika Ochotona rufescens is naturally tolerant to the analgesic effects elicited by the opium alkaloid. In spite of the different responsiveness of the two species to morphine we find that the pika brain and the rabbit brain both contain a mixture of mu-, delta- and kappa-opioid sites in nearly the same proportions: 46-47% mu, 23% delta and 28-30% kappa. Moreover, apparent binding of morphine in pika and rabbit brain membranes is inhibited in the presence of Na+ ions and/or of 5-guanylylimidodiphosphate indicating that morphine should behave as an opiate agonist (analgesic) not only in rabbits, which it does but also in pikas, which it does not.