INTERRELATIONSHIPS BETWEEN SOMATOSTATIN SST2A RECEPTORS AND SOMATOSTATIN-CONTAINING AXONS IN RAT-BRAIN - EVIDENCE FOR REGULATION OF CELL-SURFACE RECEPTORS BY ENDOGENOUS SOMATOSTATIN

Using an antipeptide antibody, we reported previously on the distribut ion of the somatostatin sst2A receptor subtype in rat brain. Depending on the region, immunolabeled receptors were either confined to neuron al perikarya and dendrites or distributed diffusely in tissue. To inve stigate the functional significance of these distribution patterns, we examined the regional and cellular relationships between somatostatin axons and sst2A receptors in the rat CNS, using double-labeling immun ocytochemistry. Light and confocal microscopy revealed a significant c orrelation (p < 0.02) between the distribution of somatodendritic sst2 A receptor immunoreactivity and that of somatostatin terminal fields, both quantitatively and qualitatively. Furthermore, in regions of soma todendritic labeling, a subpopulation of sst2A-immunoreactive cells wa s also immunopositive for somatostatin, suggesting that a subset of ss t2A receptors consists of autoreceptors. By contrast, in regions displ aying diffuse sst2A labeling only moderate to low densities of somatos tatin terminals were observed, and no significant relationship was fou nd between terminal density and receptor immunoreactivity. At the elec tron microscopic level, areas expressing somatodendritic sst2A labelin g were found by immunogold cytochemistry to display low proportions of membrane-associated, as compared with intracellular, receptors. Conve rsely, in regions displaying diffuse sst2A receptor labeling, receptor s were predominantly associated with neuronal plasma membranes, a find ing consistent with the high density of sst2 binding sites previously visualized in these areas by autoradiography. Double-labeling studies demonstrated that in the former but not in the latter regions, sst2A-i mmunoreactive somata and dendrites were heavily contacted by somatosta tin axon terminals. Taken together, these results suggest that the low incidence of membrane-associated receptors observed in regions of som atodendritic sst2A labeling may be caused by downregulation of cell su rface receptors by endogenous somatostatin, possibly through ligand-in duced receptor internalization.