5‐Hydroxytryptamine (5‐HT)4 receptors in post mortem human brain tissue: distribution, pharmacology and effects of neurodegenerative diseases

• Published in: British journal of pharmacology 1995-03, Vol.114 (5), p.993-998
• Main Authors: Reynolds, G.P., Mason, S.L., Meldrum, A., Keczer, S., Parties, H., Eglen, R.M., Wong, E.H.F.
• Format: Article
• Language: English
• Subjects: 5‐HT4 receptors; [3H]‐GR 113808; Aged; Aged, 80 and over; Alzheimer's disease; Animals; Binding, Competitive - drug effects; Biological and medical sciences; Brain Chemistry - drug effects; Brain Chemistry - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Guinea Pigs; Human brain; Humans; Huntington's disease; In Vitro Techniques; Indoles - metabolism; Kinetics; Male; Medical sciences; Middle Aged; Nerve Degeneration; Nervous System Diseases - metabolism; Neurology; Parkinson's disease; Radioligand Assay; Receptors, Muscarinic - drug effects; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Serotonin Antagonists - metabolism; Sulfonamides - metabolism
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1995.tb13303.x

1 The distribution, pharmacology and effects of neurodegenerative diseases on 5‐HT4 receptors in human brain have been characterized in vitro. 2 The 5‐HT4 receptor in post mortem human brain tissue was specifically labelled with [3H]‐GR 113808. In human putamen, this ligand labelled a homogeneous population of sites, with an apparent affinity (‐log Kd) of 10.1 and a density (Bmax) of 5.73 fmol mg−1 tissue. The pharmacology of this site was characterized by use of a series of displacing ligands, and the following rank order of apparent affinities (with mean ± s.d. ‐log Ki values in parentheses) was generated: GR113808 (10.05 ± 0.04) > SDZ 205,557 (8.65 ± 0.08)> DAU 6285 (7.95 ± 0.04) > BIMU‐1 (7.81 ± 0.06) > DAU 6215 (7.42 ± 0.23) > tropisetron (7.39 ± 0.23)> 5‐HT (7.32 ± 1.00) > BIMU‐8 (7.25 ± 0.04) > (R)‐zacopride (5.82 ± 0.04). The Hill coefficients were not significantly different from unity, consistent with an interaction at a single site. A comparison of the affinities of these compounds with those obtained from guinea‐pig striatum indicated no evidence of species differences. 3 The regional distribution of 5‐HT4 receptors was assessed by determining the density of binding sites for [3H]‐GR 113808. The distribution were as follows (with mean ± s.d. Bmax values, fmol mg−1 tissue, in parentheses): caudate nucleus (8.7 ± 1.5), lateral pallidum (8.6 ± 5.5), putamen (5.7 ± 3.0), medial pallidum (3.8 ± 0.9), temporal cortex (2.6 ± 0.6), hippocampus (2.4 ± 0.8), amygdala (2.3 ± 1.1), frontal cortex (1.7 ± 0.5), cerebellar cortex (