The pharmacology and function of 5-HT3receptors

A pharmacological analysis of receptors mediating the excitatory response to 5‐hydroxytryptamine in the guinea‐pig isolated trachea

“…These findings suggest that neuronal 5-HT3 receptors may contribute to the 5-HT-induced cholinergic response in the first phase. The inefficacy of cocaine, a compound that has antagonistic properties at 5-HT3 receptors (Fozard et al, 1979) is difficult to explain, but might reflect 5-HT3 receptors heterogeneity (Richardson & Engel, 1986). In this respect, the potent cocaine derivative antagonist, MDL 72222, was found to antagonize central but not peripheral 5-HT3 receptors (Fozard, 1984;Richardson & Engel, 1986).…”

“…The inefficacy of cocaine, a compound that has antagonistic properties at 5-HT3 receptors (Fozard et al, 1979) is difficult to explain, but might reflect 5-HT3 receptors heterogeneity (Richardson & Engel, 1986). In this respect, the potent cocaine derivative antagonist, MDL 72222, was found to antagonize central but not peripheral 5-HT3 receptors (Fozard, 1984;Richardson & Engel, 1986). Nevertheless, caution is required in interpreting our findings, since a slight reduction of the first 5-HT phase is also observed following repeated agonist curves, and because the affinity of 5-HT for 5-HT3 receptors is in the micromolar range of concentrations (Eglen et al, 1990).…”

Characterization of a human 5‐hydroxytryptamine3 receptor type A (h5‐HT3R‐AS) subunit stably expressed in HEK 293 cells

“…During the development of the first generation of 5-HT3 receptor-selective ligands, striking differences in antagonist affinities were encountered between 5-HT3 receptor-containing preparations (Fozard, 1983;1984;Richardson et al, 1985). Although this was originally thought to reflect the existence of multiple 5-HT3 receptor subtypes with tissue-dependent expression (Richardson & Engel, 1986), subsequent studies have identified inter-species differences in 5-HT3 receptor pharmacology as the principle determinant of such heterogeneity (reviewed by Peters et al, 1994). For example, the 5-HT3 receptor expressed by guineapig tissues displays atypically low affinity towards 5-HT3 receptor selective ligands and appears refractory to activation by the arylbiguanide class of agonist Newberry et al, 1991;Wong et al, 1993b;.…”

Effects of a 5‐hydroxytryptamine3 receptor antagonist (ICS 205‐930) on colonic motor activity in healthy men.

“…Activation of this receptor site occurs only at higher concentrations of 5-HT and results in the release of substance P, which in turn activates substance P receptors on smooth muscle cells and thereby causes contraction (Buchheit et at., 1985b). 5-HT3 receptors are located on afferent sensory neurons in the enteric nervous system and mediate many of the excitatory actions of 5-HT Richardson et al, 1985;Richardson & Engel, 1986). ICS 205-930 is devoid of any substantial affinity to adrenoreceptors, dopamine and histamine receptors, as well as to muscarinic receptor sites .…”