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R Sircar

Publications and source records attributed to R Sircar.

40 records · Page 3Linked to original sources

Ontogeny of sigma opiate/phencyclidine-binding sites in rat brain.

The development of stereospecific sigma opiate/phencyclidine (PCP)-binding sites in fetal and neonatal rat brain was examined. Displaceable PCP binding was detected from day 13 of gestation. Bmax values increased to adult levels just prior to birth. Apparent KD values did not change. Stereospecific binding became detectable after day 19, concomitant with a rapid increase in Bmax. Despite the early appearance of binding, pharmacologically relevant stereospecific sigma opiate/PCP-binding sites do not become evident until shortly prior to parturition.

Aging↗

Characterization of specific sigma opiate/phencyclidine (PCP)-binding sites in the human brain.

Specific [3H]phencyclidine (PCP)-binding studies were carried out in homogenates prepared from different regions of post-mortem human brains derived from subjects free of any neurological disease. Scatchard analysis revealed a single class of [3H]PCP-binding sites. Binding was found to be stereospecific i.e. markedly greater ability of the potent PCP agonist dexoxadrol to displace specifically bound 10 nM [3H]PCP as compared to its behaviorally inactive enantiomer levoxadrol. Stereospecific binding was abolished by preincubation of homogenate with trypsin or by heating the homogenate to 90 degrees C for 15 min. Various sigma opiates displaced specifically bound [3H]PCP binding in a rank order similar to that seen in rat brain. Thus a baseline has been established to enable future elucidation of the possible role of these sites in psychiatric illnesses.

Brain↗

PCP/NMDA receptor-channel complex and brain development.

Phencyclidine (PCP) acts on a variety of neurotransmitter systems--cholinergic, catechoaminergic, indoleaminergic, and peptidergic--but the dose at which it produces its psychotomimetic effects is lower than the concentration at which it affects these systems. At low doses, PCP interacts primarily with a binding site located within the ionophore associated with the NMDA receptor complex--binding to this site has been used as a biochemical marker for NMDA channel activity. PCP/NMDA receptor-channel complex has been shown to play an important role in brain development but little is known of the neurochemical effects following postnatal administration of NMDA antagonists in rats. In the present study, rats were treated with PCP from Day 5 until Day 15 after birth and binding to the PCP receptor was measured on postnatal Day 21 using [3H]MK-801; MK-801 is a more potent and specific ligand at the PCP receptor than PCP itself. Postnatal PCP administration produced specific alterations in PCP receptor binding in 21-day-old rat forebrain. There was a reduction in the high affinity component of [3H]MK-801 binding under baseline binding conditions. In the presence of both L-glutamate and glycine, [3H]MK-801 binding in PCP-treated rats increased significantly compared to baseline but did not differ from saline-treated controls. These findings suggest that chronic PCP administration in developing rats alter NMDA channel functioning which could have long-term neurobehavioral consequences.

Aging↗