Localization of five somatostatin receptors in the rat central nervous system using subtype-specific antibodies

The cloning of five members of the somatostatin receptor family, sst(1)-sst (5), as well as two isoforms of the somatostatin receptor 2, sst(2A) and ss t(2B), enabled us to generate specific anti-peptide antisera against unique sequences in the carboxyl-terminal tail of each somatostatin receptor subt ype. We used these antibodies in multicolor immunofluorescent studies aimed to examine the regional and subcellular distribution of somatostatin recep tors in adult rat brain. Several findings are notable: The cloned sst, rece ptor is primarily localized to axons, and therefore most likely functions i n a presynaptic manner. The cloned sst, receptor isoforms exhibit strikingl y different distributions, however, both sst(2A) and sat(2B) are confined t o the plasma membrane of neuronal somata and dendrites, and therefore most likely function in a postsynaptic manner. The cloned sst(3) receptor appear s to be excluded from 'classical' pre- or postsynaptic sites but is selecti vely targeted to neuronal cilia. The cloned sst(4) receptor is preferential ly distributed to distal dendrites, and therefore most likely functions pos tsynaptically. The cloned sst(5) receptor was not detectable in the adult r at brain, however, prominent sst(5) expression was found in the pituitary. Furthermore, sst(1)-containing axons either co-contained somatostatin or we re closely apposed by somatostatin-positive terminals in a regional-specifi c manner. Neuronal somata and dendrites containing either set(2A), sst(2B) or sst(4) were found to exist in close proximity, although not necessarily synaptically linked, to somatostatin-positive terminals. Together, in the c entral nervous system the effects of somatostatin are mediated by several d ifferent receptor proteins which are distributed with considerable regional overlap. However, there appears to be a high degree of specialization amon g somatostatin receptor subtypes with regard to their subcellular targeting . This subtype-selective targeting may be the underlying principal of organ ization that allows somatostatinergic modulation of neuronal activity via b oth pre- and postsynaptic mechanisms. (C) 2000 Elsevier Science Ltd. Publis hed by Editions scientifiques et medicales Elsevier SAS.