The Elusive Nature of Cerebellar Somatostatin Receptors: Studies in Rat, Monkey and Human Cerebellum

Abstract

The pharmacological profile and localization of somatostatin (SRIF) receptors were determined in rat, monkey and human cerebellum. In rat cerebellar cortex, low ss1/sst4, intermediate sst2 and very high sst3 receptor mRNA levels were found, sst1 mRNA was also expressed in the deep cerebellar nuclei. [125I]Tyr3-octreotide binding sites in cerebellar membranes correlated with recombinant sst2, but not with sst5 or sst3 receptors and were found in the molecular layer of the cerebellum. [125I]CGP 23996 (in Na+-buffer) binding in rat cerebellum correlated with sst1 or sst4, but not with sst2, sst3 or sst5 receptor binding. Similar data were obtained in rhesus monkey cerebellum. mRNAs for all five receptors were found in the granule cell layer of the human cerebellum and/or in the dentate nucleus. [125I]Tyr3-octreotide binding was strong in the molecular layer and correlated with that of recombinant sst2 receptors, but not with sst3 or sst5 receptors. [125I]CGP 23996 (in Mg++-buffer) binding was heterogeneous (about 75%. to sst2 and 25% to sst1 and/or sst4 receptors). The molecular and granular layers were equally and the dentate nucleus strongly labeled. Thus. SRIF receptors of the sst2, sst1 and/or sst4 subtype are present in the rat, monkey and human cerebellum. In the latter two species, the sst2 type appears to be predominant. Surprisingly, the high expression of sst3 receptor mRNA is not supported by radioligand binding data in any of the species studied. The reason for this discrepancy remains to be elucidated.