A study of 3H-PK 11 195 binding to “peripheral-type” benzodiazepine receptors on human lymphocytes

Ferrero, P.; Rocca, Paola; Gualerzi, Alessandro; Benna, Paolo; Enrichens, F; Olivero, G; P, Mao; Ravizza, L.; Bergamasco, B.

doi:10.1016/0022-510x(91)90071-e

Cited by 17 publications

(7 citation statements)

References 66 publications

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“…Furthermore, there was no change in pBDZr in 10 additionally patients with PD who were under similar therapy. The affinity of 2'-chloro-N-desmethyldiazepam for pBDZr in lymphocyte as well in other tissues is at least 10-fold less than that reported for diazepam (46). Although serum levels of 2'-chloro-N-desmethyldiazepam in our patients were not determined, it seems reasonable to assume that at dosages used (3-6mg/day) they should be much below the drug concentration required to bind to lymphocyte pBDZr (Ki 2.8 pM).…”

Section: Discussionmentioning

confidence: 57%

“…Tolerance to BDZ in animals has been shown to be associated with an increase in the turnover rate of DBI in the cerebral cortex (54). We recently described a significant reduction of lymphocyte pBDZr in patients with hepatic encephalopathy (46). Very high levels of DBI were found in the spinal fluid of these patients, who may reveal the abnormal GABAergic activity generally associated with the disorder (55).…”

Section: Discussionmentioning

confidence: 99%

“…** n=8 and n=7 at T, in GAD and PD groups respectively. Values are mean+SEM PK11195, Ro 5-4864 and porphyrins, and it is unaffected at pM concentrations by clonazepam and flumazenil (33,46). Other possible confounding variables were carefully controlled and the anxious population was matched as closely possible for age, sex and sampling time and storage with the healthy volunteers.…”

Section: Discussionmentioning

confidence: 99%

“…The finding that pBDZr change in GAD patients also occurs in platelets suggests that the postulate effect of DBI should be systemic. Although no measures are available for anxious subjects, levels of immunoreactive DBI-like substance(s) in plasma of normal subjects are much lower than those effective to bind to pBDZr (46,56). Hence, DBI might act through modulation of other biological substances, such its biologically active processing peptide products.…”

Section: Discussionmentioning

confidence: 99%

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Peripheral‐type benzodiazepine receptors in anxiety disorders

Rocca

Ferrero

Gualerzi

et al. 1991

Acta Psychiatr Scand

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Peripheral benzodiazepine receptors (pBDZr) were analyzed in lymphocyte membranes from patients with anxiety disorders (generalized anxiety disorder (GAD), n = 15; panic disorder (PD), n = 10; obsessive-compulsive disorder (OCD), n = 18), other mental disorders (n = 40) and 50 healthy controls, by the specific binding of 3H-PK11195. The number of binding sites (Bmax) was significantly decreased in groups with both GAD and OCD as compared with age-matched controls, by 45% and 25% respectively, whereas the binding affinity (Kd) was the same in all disorder and control groups. Conversely, no changes in binding capacity was observed in the other disorder groups and particularly in the one with PD. The abnormality in pBDZr observed in patients with GAD was restored to a normal value after long-term treatment with 2'-chloro-N-desmethyldiazepam, which also coincided with their recovery from anxiety. Our data suggest that the clinical heterogeneity in anxiety disorders might be related to different biological mechanisms and that lymphocyte pBDZr might be useful in demonstrating these differences.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Peripheral‐type benzodiazepine receptors in anxiety disorders

Rocca

Ferrero

Gualerzi

et al. 1991

Acta Psychiatr Scand

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“…The central benzodiazepine (CBZD) receptor (Braestrup and Squires, 1977; Mohler and Okada, 1977) is a component of a macromolecular complex of the gamma-aminobutyric acid (GABA) receptorkhloride channel (Barnard et al, 1987) and is thought as the primary receptor site involved in the anxiolytic and anticonvulsant effects of benzodiazepines. The peripheral type of benzodiazepine ceptor may have a critical role in hepatic encephalopathy (Ducis et al, 1989(Ducis et al, , 1990aFerrero et al, 1991;Lavoie et al, 1990), epilepsy (Benavides et al, 198413;Ducis et al, 1990b), steroidogenesis (Mukhin et al, 1989), anxiety, and the regulation of endocrine functions (Gavish et al, 1992, for a recent review).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the peripheral‐type benzodiazepine receptors in cultured astrocytes: Evidence for multiplicity

Itzhak

Baker

Norenberg

1993

Glia

103

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In mammalian brain peripheral benzodiazepine (PBZD) receptors are predominantly localized on astroglial cells. Previous studies utilizing whole membrane preparations from brain and peripheral organs of various species have indicated several distinctions between the drug-receptor interactions of the two prototypic PBZD receptor ligands, PK 11195 and Ro5-4864. The present study was undertaken to determine whether putative differences in the binding of PBZD receptor ligands in homogenates of primary astrocyte cultures can be interpreted as the labeling of PBZD receptor subtypes. Equilibrium competition and saturation binding experiments in homogenate preparations of primary astrocytes from cerebral cortex of new born rats revealed that [3H]PK 11195 labels twice the number of [3H]Ro5-4864 binding sites. Unlabeled Ro5-4864 competes for [3H]PK 11195 binding in a manner suggesting the existence of multiple PK 11195 binding sites. The competition binding experiments, using various benzodiazepines, indicate that one binding component of PK 11195 corresponds to Ro5-4864 binding sites, whereas the second is different. The latter binding site does not correspond to the central BZD receptor but displays the pharmacological properties of the PBZD receptor. Further differences between the binding of PK 11195 and Ro5-4864 in astrocytes were detected in the presence of ethanol which was more effective in inhibiting the binding of the latter. Subcellular distribution studies indicated, however, that the binding of both [3H]PK 11195 and [3H]Ro5-4864 is associated primarily with the mitochondrial fraction of astrocytes. Taken together, the present study indicates the existence of non-overlapping PBZD binding sites in astrocytes and thus suggests the existence of PBZD receptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

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