CHARACTERIZATION OF NK-3 BINDING-SITES IN RAT AND GUINEA-PIG CORTICAL MEMBRANES BY THE SELECTIVE LIGAND [H-3] SENKTIDE

We have used [H-3] Senktide, a selective Neurokinin B receptor ligand, for the characterization of NK-3 receptors in rat and guinea pig CNS membranes. Scatchard analysis of saturation binding studies in cerebral cortex membranes indicated that this ligand bound to a single site with apparent high affinity (K(D) = 4.6 +/- 1.6 and 3.1 +/- 0.37 nM, Bmax = 13.7 +/- 1.6 and 21.8 +/- 2.2 fmol/mg protein in rat and guinea pig membranes, respectively). However, in competition studies with a group of neurokinins and related peptides two different rank orders of affinities were obtained, as follows: NKB > [MePhe7]-NKB greater-than-or-equal-to Arg0-NKB greater-than-or-equal-to Senktide >> NKA > SP, in rat membranes, and [MePhe7]NKB > Senktide = NKB > Arg0-NKB >> SP > NKA, in guinea pig membranes

N-ALKYL-NOR-TROPINE ESTERS OF 2-PHENYL-CYCLOHEXENIC ACIDS AS NEW BRONCHODILATOR AGENTS - EFFECT OF STRUCTURAL AND CONFORMATIONAL MODIFICATIONS ON AFFINITY FOR MUSCARINIC RECEPTORS

A series of N-alkyl-nor-tropine esters of 2-phenyl-2-cyclohexene-1-carboxylic, 2-phenyl-cyclohexanecarboxylic, and 2-phenyl-1-cyclohexene-1-acetic acids and their quaternary ammonium salts were synthesized and evaluated for bronchodilator activity by binding assays and pharmacological tests. The in vitro and in vivo functional activity results showed that some quaternary derivatives are potent anticholinergic bronchodilator agents, and 4 compounds (14-A, 16-A, 25-A and 28-A) were selected for pharmacotoxicological evaluation. The binding data also indicated that the affinity of these compounds for the tracheal membrane muscarinic receptors is markedly affected by structural modifications of both the cationic head and the acyl moiety of the molecule. In the series of N-alkyl-nor-tropine 2-phenyl-2-cyclohexene-1-carboxylate derivatives, a rather strict limitation of the bulk of the equatorial substituent of tropine nitrogen is required for very high affinity. Conformational analysis and molecular graphics techniques evidenced an influence of the acyl moiety conformation on the affinity of the different tropinic esters, suggesting that the carbonyl oxygen may participate in interaction with the binding site, eliciting a marked increase of potency when it is oriented in a proper conformation with respect to the tropinic nitrogen and the phenyl ring

Stereoselective inhibition of muscarinic receptor subtypes by the eight stereoisomers related to rociverine.

The chemical structure corresponding to 1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid 2-(diethylamino)-1-methylethyl ester has the classical profile of ester-type antimuscarinic drugs. The presence of three chiral carbons leads to eight stereoisomers and the substitutions on the cyclohexyl ring generate cis-isomers (1, named rociverine) and trans-isomers (2). The aim of this study was to determine the binding pattern of the eight stereoisomers and two derived compounds, (1S,2S)-1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid 2-(dimethylamino)-1-ethyl ester (3) (1S,2S)-1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid (S)-2-(diethylamino)-1-methylethyl ester methyl iodide (4), at the five cloned muscarinic receptors stably expressed in chinese hamster ovary cells, in order to define how stereochemical modifications could affect the affinity. Our data showed that cis-stereoisomers exhibited higher variations in affinity than trans-stereoisomers. Among the cis-stereoisomers, those with the (1R,2R) configuration showed considerably higher affinities (up to 240-fold) than those with the (1S,2S) configuration. The (1S,2S) configuration was important for binding selectivity; this was confirmed also by the use of the two additional compounds

Facilitating information system development with panoramic view on data

Can ideology, as a widespread "expectation creator," impact economic decisions? In two studies we investigated the influence of the Benevolent Sexism (BS) ideology (which dictates that men should provide for passive and nurtured women) on women's economic decision-making. In Study 1, using a Dictator Game in which women decided how to share amounts of money with men, results of a Generalized Linear Mixed Model analysis show that higher endorsement of BS and contextual expectations of benevolence were associated with more very unequal offers. Similarly, in an Ultimatum Game in which women received monetary offers from men, Study 2's Generalized Linear Mixed Model's results revealed that BS led women to reject more very unequal offers. If women's endorsement of BS ideology and expectations of benevolence prove contrary to reality, they may strike back at men. These findings show that BS ideology creates expectations that shape male-female relationships in a way that could be prejudicial to men