PubMed · 5073772
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T V Harry, D J Richards. 1972. Lorazepam--a study in psychomotor depression.. https://pubmed.ncbi.nlm.nih.gov/5073772/
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Sequential reverse transcription and polymerase chain reaction (RT-PCR) of the mRNA were used to investigate the expression of dopamine receptors in human peripheral blood lymphocytes. The RT-PCR products contained three types of sequences, each corresponding to those of the D5 dopamine receptor gene and the two related pseudogenes. The lymphocyte cDNA library also contained the clones encoding parts of the three genes. Binding profiles of dopaminergic ligands to the lymphocytes were similar to those for the native neuronal membranes.
The title compound contains the tetracyclic A-B-C-E ring system of cephalotaxus alkaloids. Unexpectedly, the five-membered-ring plane is twisted 67.2 degrees from the aromatic ring plane and, like cephalotaxine, the seven-membered ring is oriented in a boat form with the nitrogen at the prow.
A series of group-specific modifying reagents were tested for their effects on [3H]SCH23390 binding to brain D1 dopamine receptors in order to identify amino acid residues at the ligand binding site of the D1 dopamine receptor that are critical for ligand binding. The dependence of ligand binding on the pH of the incubation medium was also examined. The histidine-selective reagent, diethylpyrocarbonate did affect ligand binding but this is probably not due to an effect at the ligand binding site. Experiments with N-acetylimidazole and ethylacetimidate indicated that modification of tyrosine and amino residues did not exert major influences at the ligand binding site. The use of the thiol dithiothreitol indicated that breakage of a disulphide bond altered ligand binding, probably by affecting the receptor conformation, and the use of the sulphydryl reagent 5,5'-dithio-bis-nitrobenzoic acid showed that modification of a sulphydryl group on the receptor inhibited ligand binding. The carboxyl reagent N,N'-dicyclohexyl carbodiimide (DCCD) potently inhibited ligand binding and the effect could be prevented by occupancy of the receptor site by an agonist or antagonist so that there is an important carboxyl group at the receptor binding site. The total number of D1 receptors was reduced after the modification by DCCD and 70% of the residual receptors showed a reduced affinity for binding [3H]SCH23390, the remainder having the same affinity as untreated receptors. [3H]SCH23390 binding is also reduced by a decrease of pH and this effect seems to depend on the protonation of a group of pKa 6.9. Saturation analysis of [3H]SCH23390 binding performed at pH 7.5 shows a single class of high affinity sites whereas at pH 6.0, two classes of sites with higher and lower affinities are seen. These studies suggested a model whereby [3H]SCH23390 binding is to two receptor isoforms with different pH dependencies for [3H]SCH23390 binding.