Evidence for the existence of receptor--receptor interactions in the central nervous system. Studies on the regulation of monoamine receptors by neuropeptides.

Substance P (SP) (10(-8) M) can rapidly reduce the affinity and increase the density of 3H-5-HT binding sites in spinal cord membranes. CCK-8 and CCK-4 (10(-8) M) can rapidly and differentially change the characteristics of 3H-spiperone striatal binding sites linked to DA receptors of the D2 type. CCK-4 increase and CCK-8 reduce the number of striatal binding sites for 3H-spiperone, indicating for the first time separate CCK-4 binding sites. CCK-4 (10(-8) M) but not CCK-8 (10(-8) M) can rapidly reduce the affinity and increase the number of the 3H-spiperone binding sites linked to 5-HT receptors of the dorsal cerebral cortex of rats. CCK-8 (10(-8) M) only produces a trend for a small increase in the Bmax values of these receptors. These results again imply the existence of separate CCK-4 binding sites in this case in the cerebral cortex. Glutamate (10(-6) M), but not N-methyl-D-aspartate (10(-6) M) can rapidly change the characteristics of the 3H-N-propylnorapomorphine (3H-NPA) binding sites in striatal membranes of rats. Glutamate (10(-6) M) increases the density and especially reduces the affinity of the 3H-NPA binding sites, which label D2 and D3 types of DA receptors. Taken together the present findings give evidence that neuropeptide receptors and glutamate receptors can in vitro rapidly modulate the characteristics of different types of DA and 5-HT receptors by way of receptor--receptor interactions at the comodulate level or at the local circuit level. It is hypothesized that these receptor--receptor interactions are of importance for the encoding of short-term memory.