Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The binding potencies for the putative M2-selective antagonist himbacine were determined in radioligand binding and in functional response assays in neuronal tissue and Chinese hamster ovary cells containing transfected muscarinic receptors. Himbacine was shown to bind to all five cloned muscarinic receptor subtypes in the order of potencies: hM2 = hM4 > hM3 > hM1 > hM5 (Kd values were 4, 7, 59, 83 and 296 nM, respectively). Himbacine was shown to bind to M2 receptors in rat heart and brain stem with Kd values of 6.9 and 4.6 nM, respectively. In rat brain tissues with complex mixtures of muscarinic receptors, and using the radioligand [3H] +/- -5,11-dihydro-11-([(2-(2-[(dipropylamino)methyl]-1- peperidinyl)ethyl)amino]carbonyl)-6H-pyrido(2,3-b)(1,4)benzodiazep ine-6-one to demarcate M2 and M4 receptors, himbacine was shown to bind to 80% of cortical or striatal receptors with Kd values of 4.5 and 3.8 nM, respectively, consistent with the involvement of M2 and/or M4 receptors in both these brain regions. Himbacine was a potent blocker of oxotremorine-M-mediated cyclic AMP inhibition in rat striatum (4.4 nM) and in N1E-115 neuroblastoma cells (10.6 nM), responses mediated by M4 receptors. Himbacine also reversed oxotremorine-M-mediated inhibition of evoked acetylcholine release from hippocampal tissue with a Kd value of 8.6 nM, a value consistent with the involvement of M2 or M4 receptors. At the cortical postsynaptic muscarinic receptors involved with phosphoinositide turnover (putative M1 and M3 receptors), himbacine was 21-fold less potent. Himbacine appears to be a potent muscarinic antagonist that displays selectivity for M2 or M4 receptors, as compared to M1 or M3 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Binding and functional selectivity of himbacine for cloned and neuronal muscarinic receptors. 133 10

To compare the proportions of four muscarinic receptors in different rat brain regions, we used competition curves with four selective antagonists, at 1-[N-methyl-3H]scopolamine methyl chloride [( 3H]NMS) binding equilibrium and after allowing [3H]NMS dissociation for 35 min. Himbacine and methoctramine were shown to discriminate two muscarinic receptor subtypes having a high affinity for 4-diphenylacetoxy-N-methylpiperidine methiodide and hexahydrosiladifenidol, intermediate affinity for pirenzepine, and low affinity for AF-DX 116. One M4 subtype had a high affinity for himbacine and methoctramine; it was found predominantly in homogenates from rat striatum (46% of total [3H]NMS receptors) and in lower proportion in cortex (33% of [3H]NMS receptors) and hippocampus (16% of [3H]NMS receptors). Its binding properties were identical to those of muscarinic receptors in the neuroblastoma x glioma NG 108-15 hybrid, suggesting that it was encoded by m4 mRNA. The M3 subtype (typically found in rat pancreas, a tissue expressing the m3 mRNA) had a low affinity for himbacine and methoctramine and represented about 10% of all [3H]NMS receptors in rat brain cortex, hippocampus, striatum, and cerebellum. M1 and M2 receptors were identified in rat brain by their high affinity for pirenzepine and AF-DX 116, respectively.
 ...
PMID:Binding of selective antagonists to four muscarinic receptors (M1 to M4) in rat forebrain. 238 34