Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An autoradiographic analysis of high-affinity binding sites for the vesicular acetylcholine transport blocker [3H]vesamicol (2-(4-phenylpiperidino) cyclohexanol; AH 5183) was conducted in rat brain. [3H]Vesamicol binding was displaced 52-99% by DPPN [( 2,3,4,8]-decahydro-3-(4-phenyl-1-piperidinyl)-2-napthalenol) (IC50 = 14 nM) and by ketanserin (500 nM), haloperidol (43 nM), and vesamicol analogs, but not by drugs selective for adenosine, adrenergic, amino acid, calcium channel, monoaminergic, opioid, PCP, sigma, or several other receptor classes. [3H]Vesamicol binding was most concentrated in the interpeduncular nucleus and fifth and seventh cranial nerve nuclei. Moderate binding was found in the lateral caudate-putamen, medial nucleus accumbens, olfactory tubercle, vertical and horizontal diagonal bands of Broca, and basolateral amygdala. The distribution of [3H]vesamicol binding was similar to distributions of acetylcholine (r = 0.88), acetylcholine esterase (r = 0.97), choline acetyltransferase (ChAT) (r = 0.97), and [3H]hemicholinium-3 binding sites (r = 0.95-0.99). Lower correlations were obtained between [3H]vesamicol and muscarinic receptor densities (r = 0.50-0.70). Few exceptions to the match between binding and cholinergic neuronal markers were found, e.g., the molecular layer of the cerebellum and the thalamus. Lesions of cholinergic neuronal projections to the neocortex or hippocampus reduced [3H]vesamicol binding in each of these regions, but to a lesser extent than reductions in ChAT. [3H]Vesamicol binding sites appear to be anatomically associated with brain cholinergic neurons, a locus that is consistent with the control by this site of vesicular acetylcholine uptake.
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PMID:[3H]vesamicol binding in brain: autoradiographic distribution, pharmacology, and effects of cholinergic lesions. 297 45

This study examined the effects of subsequent, subchronic, treatment with choline uptake enhancer MKC-231 on the behavioral and cellular deficits induced by repeated PCP exposure in rats. Prior subchronic PCP exposure resulted in increased locomotion following an acute PCP or cocaine challenge, but resulted in decreased locomotor activity in response to a carbachol-challenge. MKC-231 significantly antagonized the alterations in the locomotor responses to cocaine and carbachol, but not to PCP. In the novel object recognition test, repeated PCP exposure caused cognitive deficits in rats, and the PCP-induced cognitive deficits were antagonized by MKC-231. In contrast, no effects of PCP exposure were shown in the repeated passive avoidance test. Furthermore, repeated PCP exposure decreased a number of choline acetyltransferase (ChAT)-positive cells in the medial septum and increased dynorphin A expression in the ventral striatum. Moreover, MKC-231 significantly antagonized the changes in septal ChAT-positive cells, but not the changes in ventrostriatal dynorphin A expression. These results suggest that MKC-231 could be a therapeutic drug for the treatment of schizophrenia.
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PMID:Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats. 1746 60