Differential distribution of somatostatin receptor subtypes in rat brain revealed by newly developed somatostatin analogs.

Somatostatin receptor subtypes were labeled with the somatostatin analogs 125I]CGP 23996 and 125I]MK 678 and the distribution of these receptors in rat brain was investigated using quantitative autoradiographic techniques. 125I]CGP 23996 and 125I]MK 678 specifically label different populations of somatostatin receptors in rat brain. In a number of brain regions striking differences in the distribution of the somatostatin receptor subtypes labeled by each peptide were observed. High levels of binding sites for both 125I]CGP 23996 and 125I]MK 678 were present in the cerebral cortex, CA1 region and subiculum of the hippocampus. In contrast, high levels of 125I]MK 678 binding were found in the dentate gyrus of the hippocampus while few 125I]CGP 23996 binding sites were observed in this brain region. 125I]CGP 23996 binding was detected in the central region of the interpeduncular nucleus whereas the dorsal and lateral subnuclei of this brain area expressed mainly somatostatin receptors with high affinity for MK 678. The locus coeruleus and regions of the superior colliculus and hypothalamus selectively express 125I]MK 678-sensitive somatostatin receptors. Furthermore, limbic structures such as the lateral septum, the nucleus accumbens and ventromedial striatum had much higher levels of 125I]MK 678 binding sites than 125I]CGP 23996 binding sites. Differences in the expression of the somatostatin receptor subtypes were also detected in the substantia nigra. 125I]CGP 23996 binding was present in the pars reticulata but not the pars compacta whereas the reverse distribution for 125I]MK 678 binding sites was observed. The differential distribution of 125I]CGP 23996 and 125I]MK 678 binding sites in rat brain supports the hypothesis that these peptides selectively label different somatostatin receptor subtypes in the central nervous system.