A comparative autoradiographic study of the distributions of substance P and eledoisin binding sites in rat brain

Abstract

The relative potencies tachykinin peptide analogs competing for binding of [ 125I]Bolton Hunter-conjugated substance P ([ 125I]BH-SP) or [ 125I]Bolton Hunter-conjugated eledoisin ([ 125I]BH-ED) in slide-mounted rat brain sections are very different, indicating the presence of two distinct tachykinin binding sites. The structure-activity profiles resemble those described in peripheral bioassay studies in which two tachykinin receptors have been postulated. Autoradiography of the two iodinated ligands bound with selective and one-site in vitro incubation conditions shows two discrete and distinctly different distribution patterns in brain. Binding sites for [ 125I]BH-ED are densely distributed in the accessory olfactory bulb, intermediate layers of the cerebral neocortex, portions of the hippocampal CA fields, hypothalamic supraoptic and paraventricular nuclei, central portions of the interpenduncular nucleus, sphenoid nucleus, medial subdivision of the solitary tract complex, and the substantia gelatinosa of the spinal cord. Binding sites for [ 125I]BH-SP are present in many of these same structures, but the densities and distribution patterns are different. In addition, [ 125I]BH-SP binds in numerous structures not labeled by [ 125I]BH-ED. Neither pattern matches the locations of terminations of endogenous tachykinin pathways marked by immunohistochemistry. The results suggest that it would be inappropriate to name brain tachykinin receptors according to the endogenous ligand which binds with highest affinity.