Assessment of the pharmacological properties of 5-methoxyindole derivatives at 5-HT4 receptors.

Objectives: The aim was to examine the biological activity of 5-methoxytryptamine derivatives at the 5-hydroxytryptamine (5-HT)(4) receptor to explore the effect of substitution on the aliphatic amine of the 5-methoxyamine scaffold.

Methods: Three compounds were tested for affinity at the 5-HT(4) receptor by radioligand binding and functional activity using guinea-pig ileum and human colon circular muscle preparations and also in the mouse whole gut transit test.

Key Findings: The three compounds all had agonist properties at the 5-HT(4) receptor but their efficacy differed in the different functional tests.

Altered dopamine receptor and dopamine transporter binding and tyrosine hydroxylase mRNA expression following perinatal NMDA receptor blockade.

This study examined how perinatal phencyclidine (PCP) treatment would affect dopamine D2 receptor and dopamine transporter (DAT) binding at different stages after treatment cessation. Female rat pups received injections of PCP (10 mg/kg, s.c.

Effect of chronic treatment with clozapine and haloperidol on 5-HT(2A and 2C) receptor mRNA expression in the rat brain.

This study examined regional changes of 5-HT(2A and 2C) receptor mRNA expression in the rat brain after chronic administration of clozapine (1.5 mg/kg/day) and haloperidol (2.0 mg/kg/day) for 36 days.

Decreased plasma peptide YY accompanied by elevated peptide YY and Y2 receptor binding densities in the medulla oblongata of diet-induced obese mice.

It is well known that the peripheral peptide YY (PYY)-central neuropeptide Y (NPY) Y2 receptor axis plays an important role in promoting negative energy balance regulation. Both the hypothalamus and medulla oblongata express a high level of Y2 receptors; however, the functional role of this receptor in chronic high-fat diet-induced obesity has not been fully examined. Using quantitative autoradiography, this study measured binding densities of total [(125)I]PYY and Y2 receptors in the hypothalamus and medulla of chronic high-fat diet-induced obese (DIO), obese-resistant, and low-fat-fed mice.

Comparison of 5-HT4 and 5-HT7 receptor expression and function in the circular muscle of the human colon.

Serotonin receptors are potential targets for treating functional bowel disorders. This study investigated the functional roles and expression of the 5-HT4 and the 5-HT7 receptor, which coexist in human colon circular smooth muscle. 5-HT3 receptor expression was also investigated.

Optimization of a pharmacophore model for 5-HT4 agonists using CoMFA and receptor based alignment.

Twenty two 5-HT4 agonists obtained from our laboratory and the recent literature were used to develop a CoMFA model to predict 5-HT4 agonist activity. Two models were produced and compared for predictivity, the first by alignments based on atom overlapping (model A) and the second by adding agonist binding site interacting points of the 5-HT4 receptor (model B). Comparison of the two models showed that the q2 value for model A was 0.

Structural requirements for the interaction of sheep insulin-like factor 3 with relaxin receptors in rat atria.

Relaxin is a peptide with various reproductive and nonreproductive functions. The site for the peptide-receptor interaction contains two arginines (Arg) and an isoleucine (Ile) or valine (Val) residue in the B-chain with a configuration of -Arg-X-X-X-Arg-X-X-Ile/Val-X-. The sheep insulin-like peptide 3 (INSL3), a structural homologue of relaxin, also contains the n, n+4 arginines in the B-chain but they are displaced towards the carboxyl terminus by four residues (-X-X-X-X-Arg-X-X-Val-Arg-).