Quantitative radioautographic study of somatostatin receptors heterogeneity in the rat extrahypothalamic brain

The possible heterogeneity of extrahypothalamic somatostatin receptors was studied in rat brain by quantitative radioautography. The respective distribution and relative proportion of two somatostatin receptor sub-types (SS1 and SS2) were assessed by using two radioligands, the non-selective probe [125I]Tyr3-D-Trp8-somatostatin14 and the SS1 selective analogue [125I]Tyr3-SMS 201-995. For both ligands, adjacent brain sections were processed in the presence of micromolar concentrations of either a non-discriminative competitor (somatostatin14) or SS1-selective analogue (SMS 201-995). The comparative analysis of the specific binding remaining in the presence of each non-radioactive competitor permitted a semi-quantitative analysis of the proportion of SS1 and SS2 receptor sub-types in each brain region examined. Data obtained correlate well with homogenate binding results reported previously [Reubi J. C. (1984) Neurosci. Lett. 49, 259-263]. Although the distribution patterns obtained with both radioligands were similar, [125I]Tyr3-SMS 201-995 labelled only a fraction of [125I]Tyr0-D-Trp8-somatostatin14-labelled sites in certain brain regions. For example, both superficial and deep cortical laminae, as well as the basolateral amygdaloid nucleus and CA1 hippocampal area exhibited different binding densities with [125I]Tyr0-D-Trp8-somatostatin14 depending on the competitor used in the assay (somatostatin14 or SMS 201-995). On the other hand, [125I]Tyr3-SMS 201-995 binding was eliminated in an identical fashion by either competitor in these very same brain areas. This suggests the existence of SS1 and SS2 somatostatin receptor sub-types in these regions. In all other brain areas examined, somatostatin receptor sites are apparently of the SS1 sub-type. The heterogeneity of somatostatin receptors observed in certain regions may have relevance for the various biological effects induced by somatostatin in the central nervous system.