Multiple tachykinin receptors in guinea pig brain. High densities of substance K (neurokinin A) binding sites in the substantia nigra.

Receptor binding characteristics of labelled substance P (SP) and substance K (SK) were investigated in guinea pig membrane preparations and by in vitro receptor autoradiography. The two ligands bind to single class of sites with Kd of 2.1 nM and Bmax of 37.0 fmol/mg protein for SP and 10.6 nM and 50.3 fmol/mg protein for SK. Ligand selectivity patterns markedly differ for the two ligands. On SP binding sites, SP greater than physalaemin greater than eledoisin greater than SK greater than kassinin greater than Neuromedin K. On the other hand, SK greater than kassinin greater than Neuromedin K greater than eledoisin greater than SP greater than physalaemin on SK binding sites. The autoradiographic distribution of SP and SK binding sites is also different. While the cerebral cortex, substantia nigra and cerebellum contain very low to low densities of SP sites, they are all rich in SK binding sites. These data clearly demonstrate the existence of at least two classes of tachykinin binding sites in guinea pig brain. Moreover, the high density of SK binding sites present in the substantia nigra suggests possible physiological roles for SK in this region.