AUTORADIOGRAPHIC CHARACTERIZATION OF [H-3] 5-HT-MODULINE BINDING-SITES IN RODENT BRAIN AND THEIR RELATIONSHIP TO 5-HT1B RECEPTORS

5-HT-moduline is an endogenous tetrapeptide [Leu-Ser-Ala-Leu (LSAL)] t hat was first isolated from bovine brain tissue, To understand the phy siological role of this tetrapeptide,,ve 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) indic ated that [H-3]-5-HT-moduline bound specifically to rat brain sections with high affinity (K-d = 0.77 nM and B-max = 0.26 dpm/mm(2)), Using film autoradiography in parallel, we found that 5-HT-moduliae binding sites were expressed in a variety of rat and mouse brain structures. I n 5-HT1B receptor knock-out mice, the specific binding of [3H]5-HT-mod uline was not different from background labeling, indicating that 5-HT -moduline targets are exclusively located on the 5-HT1B receptors. Alt hough the distribution of 5-HT-moduline binding sites was similar to t hat of 5-HT1B receptors, they did not overlap totally. Differences in distribution patterns were found in regions containing either high lev els of 5-HT1B receptors such as globus pallidus and subiculum that wer e poorly labeled or in other regions such as dentate gyrus of hippocam pus and cortex where the relative density of 5-HT-moduline binding sit es was higher than that of 5-HT1B receptors. In conclusion, our data, based on autoradiographic localization, indicate that 5-HT-moduline ta rgets are located on S-HT1B receptors present both on 5-HT afferents a nd postsynaptic neurons. By interacting specifically with 5-HT1B recep tors, this tetrapeptide may play a pivotal role in pathological states such as stress that involves the dysfunction of 5-HT neurotransmissio n.