Autoradiographic characterization of [ super(3)H]-5-HT-moduline binding sites in rodent brain and their relationship to 5-HT sub(1B) receptors

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-09, Vol.94 (18), p.9899-9904
• Main Authors: Cloeez-Tayarani, I, Cardona, A, Rousselle, J-C, Massot, O, Edelman, L, Fillion, G
• Format: Article
• Language: English
• Subjects: Rodentia
• ISSN: 0027-8424

5-HT-moduline is an endogenous tetrapeptide [Leu-Ser-Ala-Leu (LSAL)] that was first isolated from bovine brain tissue. To understand the physiological role of this tetrapeptide, we studied the localization of 5-HT-moduline binding sites in rat and mouse brains. Quantitative data obtained with a gaseous detector of beta -particles ( beta -imager) indicated that [ super(3)H]-5-HT-moduline bound specifically to rat brain sections with high affinity (K sub(d) = 0.77 nM and B sub(max) = 0.26 dpm/mm super(2)). Using film autoradiography in parallel, we found that 5-HT-moduline binding sites were expressed in a variety of rat and mouse brain structures. In 5-HT sub(1B) receptor knock-out mice, the specific binding of [ super(3)H]-5-HT-moduline was not different from background labeling, indicating that 5-HT-moduline targets are exclusively located on the 5-HT sub(1B) receptors. Although the distribution of 5-HT-moduline binding sites was similar to that of 5-HT sub(1B) receptors, they did not overlap totally. Differences in distribution patterns were found in regions containing either high levels of 5-HT sub(1B) receptors such as globus pallidus and subiculum that were poorly labeled or in other regions such as dentate gyrus of hippocampus and cortex where the relative density of 5-HT-moduline binding sites was higher than that of 5-HT sub(1B) receptors. In conclusion, our data, based on autoradiographic localization, indicate that 5-HT-moduline targets are located on 5-HT sub(1B) receptors present both on 5-HT afferents and postsynaptic neurons. By interacting specifically with 5-HT sub(1B) receptors, this tetrapeptide may play a pivotal role in pathological states such as stress that involves the dysfunction of 5-HT neurotransmission.