[3H]5-Hydroxytryptamine binding sites: species and tissue variation.

The characteristics of spiperone inhibition of [3H]5-hydroxytryptamine [(3H]5-HT; [3H]serotonin) binding were examined in dorsal (DH) and ventral (VH) hippocampus, corpus striatum (CS) or caudate nucleus (CN), and frontal cortex (FC) in the rabbit, guinea pig, and cat. Some of the properties of spiperone inhibition of [3H]5-HT binding in these species were similar to the properties previously found in the rat. Spiperone was significantly more potent in DH, VH, and FC than in CS or CN. It produced shallow or biphasic inhibition curves, resulting in Hill slopes of less than 1.0. Nonlinear regression analysis of the data showed that the inhibition curves fit a two-site binding model significantly better than a one-site model in each brain region. The dissociation constants of spiperone for the high-affinity binding site (KH) for all the tissues and species, except cat FC and rabbit DH, were very close to those previously found in the rat (2-13 nM). However, the dissociation constants for the low-affinity binding site (KL) were different from those in the rat in all species and tissues examined, except cat FC and CS. The present data are consistent with the concept of multiple 5-HT1 binding sites and suggest the presence of at least two, and perhaps as many as three, groups of sites in the mammalian brain.