Are 5-hydroxytryptamine sub(7) receptors involved in [ super(3)H]5-hydroxytryptamine binding to 5-hydroxytryptamine sub(1nonA-nonB) receptors in rat hypothalamus?

• Published in: Molecular pharmacology Vol. 49; no. 3; pp. 556 - 559
• Main Authors: Gobbi, M, Parotti, L, Mennini, T
• Format: Journal Article
• Language: English
• Published: 01.03.1996
• ISSN: 0026-895X

We assayed [ super(3)H]5-hydroxytryptamine ([ super(3)H]5-HT) binding in rat hypothalamic membranes to confirm the possibility of measuring 5-HT sub(7) receptors. Binding was tested in the presence of 3 mu M ( plus or minus )-pindolol, a concentration higher than previously suggested for the same purpose (0.1 mu M). This higher concentration was, however, needed to fully saturate 5-HT sub(1A) and 5-HT sub(1B) receptors without interaction with 5-HT sub(7) receptors. Under these conditions, [ super(3)H]5-HT binding could be further inhibited with methiothepin (used to determine nonspecific binding) and with 5-HT, with an IC sub(50) of 1.4 nM and a slope of 1. The inhibition curves of ( plus or minus )-8-hydroxy-dipropylaminotetralin, ritanserin, and mianserin were shallow (slopes, 0.35-0.58) and could be better analyzed with the two-site model, indicating that the pindolol-insensitive [ super(3)H]5-HT binding sites in rat hypothalamic membranes are heterogeneous. Although the IC sub(50) of the compounds tested suggests that one population of sites is actually associated with 5-HT sub(7) receptors, our data clearly indicate that this binding assay does not selectively label 5-HT sub(7) receptors in native tissues. These results challenge a previous report and suggest that the proposed down-regulation of 5-HT sub(7) receptors after fluoxetine treatment should be considered with caution. The development of more selective and sensitive binding assays will probably offer significant advantage.