Search results for "Radioligand Assay"
showing 9 items of 39 documents
Probing human beta1- and beta2 -adrenoceptors with domain-specific fusion protein antibodies.
1997
In order to generate antibodies suitable for immunological studies on beta-adrenoceptors constitutively expressed at low levels in cells or tissues we have produced fusion proteins of the amino- and carboxy-terminus, and the second extracellular loop of the human beta 1- or beta 2-adrenoceptors with bacterial glutathione-S-transferase in E. coli. Rabbit antibodies raised against these fusion proteins strongly reacted with intact human beta 1- or beta 2-adrenoceptors in a subtype- and domain-specific manner. Antibodies directed against the second extracellular loop of the beta 1-adrenoceptor reacted stronger with non-denatured receptors and decreased the affinity of the 3H-labelled antagonis…
Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization.
2007
Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
In vitro affinities of various halogenated benzamide derivatives as potential radioligands for non-invasive quantification of D(2)-like dopamine rece…
2007
Abstract Benzamide derivatives as radiotracers have played an important role in diagnosing malfunction in dopaminergic neurotransmission. A variety of halogenated and two unsubstituted benzamide derivatives were synthesised and their in vitro affinities to dopaminergic, serotonergic and adrenergic receptors and their lipophilicities were determined. As references IBZM (3), raclopride (4) and FLB457 (5) were tested as well. The two iodinated compounds NAE (27) and NADE (28) displayed Ki values of 0.68 and 14 nM for the D2 receptor. The well-established radiotracers FP (1) and DMFP (2) showed affinities in the same range as did the brominated compounds NABrE (29) and NABrDE (30). The log D7.4…
Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopami…
2005
A series of 6alpha- and 6beta-substituted benztropines were synthesized. A marked enantioselectivity was observed for the 6beta-methoxylated benztropines, the (1R)-isomers being more potent than the corresponding (1S) compounds. The racemic 6alpha-methoxy-3-(4',4' '-difluorodiphenylmethoxy)tropane (5 g) was the most potent compound. It has been found that modifications at the 6-position of benztropine might reduce the DAT binding affinity, maintaining otherwise a significant dopamine uptake inhibitory activity. A reinvestigation of the absolute configuration of 6beta-methoxytropinone proved the 6R configuration for the (+)-enantiomer.
Inhibition of B2 receptor internalization delays its dephosphorylation
1997
Structure-activity relationships of dimethindene derivatives as new M2-selective muscarinic receptor antagonists.
2003
A series of 2,3-disubstituted indenes, which are analogues of the widely used histamine H(1) receptor antagonist dimethindene, have been synthesized and studied as muscarinic and histamine receptor antagonists. The affinities of these compounds for the five human muscarinic receptor subtypes (M(1)-M(5)) and for human histamine H(1) receptors were determined in radioligand binding studies using membranes from transfected Chinese hamster ovary (CHO) cells and [(3)H]N-methylscopolamine ([(3)H]NMS). The results demonstrate that the diisopropyl analogue 19 has a similar high affinity as (S)-dimethindene at M(2) receptors ((S)-dimethindene: pK(i) = 7.52; (-)-19: pK(i) = 7.37) with an improved sel…
Variations of vitamin D-like reactivity in the crustacean Orchestia cavimana during the molt cycle
1991
An investigation into vitamin D-like molecules has been performed on whole extracts of the terrestrial amphipod Orchestia cavimana, using a sensitive nonequilibrium assay employing 1,25-(OH)2 D receptor from calf thymus. Relatively large amounts of these secosteroid-like molecules were observed and they varied in concentration according to the stages of the molt cycle. The amplitude of these variations reaches a ratio of about 40 from the minimum in premolt to the intermolt sharp peak.
Cloning of two melanocortin (MC) receptors in spiny dogfish
2004
We report the cloning and characterization of two melanocortin receptors (MCRs) from the spiny dogfish (Squalus acanthias) (Sac). Phylogenetic analysis shows that these shark receptors are orthologues of the MC3R and MC5R subtypes, sharing 65% and 70% overall amino acid identity with the human counterparts, respectively. The SacMC3R was expressed and pharmacologically characterized in HEK293 cells. The radioligand binding results show that this receptor has high affinity for adrenocorticotropic hormone (ACTH)-derived peptides while it has comparable affinity for alpha- and beta-melanocyte stimulating hormone (MSH), and slightly lower affinity for gamma-MSH when compared with the human ortho…
Localization of the bradykinin B2 receptor in uterus, bladder and Madin-Darby canine kidney cells
1997
Kinins are biologically active peptides that act through specific receptors, B1 and B2. Here we describe the localization of the bradykinin B2 receptor in Madin-Darby canine kidney cells and in the uterus and urinary bladder of rat or human origin. We discuss the suitability of anti-peptide antibodies to assess the tissue distribution of bradykinin B2 receptors.