Immunohistochemical localization of the somatostatin sst2(b) receptor splice variant in the rat central nervous system.

Somatostatin is a neuromodulator in the mammalian CNS. To date, genes for at least five different somatotrophin release inhibiting factor receptors, termed sst1-sst5, have been cloned. The rat sst2 receptor exists in two splice variants, sst(alpha)a) and sst2(b), which differ in their carboxy-termini. When heterologously expressed in Chinese hamster ovary-K1 cells, these splice variants show little difference in their operational characteristics. Recently, the distribution of the sst2(a) receptor was documented, yet at present no data are available about the distribution of the sst2(b) receptor in the CNS. Here, we present the characterization of a novel polyclonal anti-peptide antibody that is selective for the sst2(b) receptor splice variant. The antibody was raised against the unique intracellular carboxy-terminal portion of the receptor protein. Using this affinity-purified antibody in western blotting experiments, the sst2(b) receptor expressed in Chinese hamster ovary-K1 cells was shown to be a glycoprotein with a molecular weight centred at about 85,000. The antibody showed no cross-reactivity to any of the recombinant human sst1-5 receptors, the rat sst2(a) receptor or wild-type Chinese hamster ovary-K1 cells. Employing immunohistochemistry, we investigated the distribution of the sst2(b) receptor in the brain and spinal cord of adult rats. A distinct distribution was found throughout the rostrocaudal axis of the CNS. Somatodendritic as well as axonal staining was observed. Somatodendritic labelling was particularly obvious in the olfactory bulb, cerebral cortex, hippocampal formation, mesencephalic trigeminal nucleus and cerebellum, as well as in cranial and spinal motor areas. The results show that the distribution of the sst2(b) receptor partially overlaps with that of the sst2(b) receptor, although there were differences in a number of brain areas. The location of the sst2(b) receptor implies that it may mediate a modulatory role of somatostatin inhibitory releasing factor on sensory as well as motor functions.