In vivo internalization of the somatostatin sst2A receptor in rat brain: Evidence for translocation of cell-surface receptors into the endosomal recycling pathway

To determine whether cellular compartmentalization of somatostatin receptor s can be regulated in vivo, we examined the immunocytochemical distribution of the sst2A receptor (sst2AR) after stereotaxical injections of somatosta tin analogs into the rat parietal cortex. Whereas CH-275, a sst1R agonist, failed to induce changes in the diffuse sst2AR immunostaining pattern chara cteristic of control animals, somatodendritic profiles displaying intracyto plasmic immunoreactive granules became apparent short-term after injection of either somatostatin or the sst2R agonist octreotide. Confocal microscopy revealed that 90% of sst2AR-immunoreactive endosome-like organelles displa yed transferrin receptor immunoreactivity. At the electron microscopic leve l, the percentage of sst2AR immunoparticles dramatically decreased at the p lasmalemma of perikarya and dendrites after octreotide injection. Conversel y, it significantly increased in endosomes-like organelles. These results d emonstrate that sst2ARs undergo, in vivo, rapid and massive internalization into the endocytic recycling compartment in response to acute agonist stim ulation and provide important clues toward elucidating somatostatin recepto r signaling in the mammalian brain.