THE ELUSIVE NATURE OF CEREBELLAR SOMATOSTATIN RECEPTORS - STUDIES IN RAT, MONKEY AND HUMAN CEREBELLUM

The pharmacological profile and localization of somatostatin (SRIF) re ceptors were determined in rat, monkey and human cerebellum. In rat ce rebellar cortex, low sst(1)/sst(4), intermediate sst(2) and very high sst(3) receptor mRNA levels were found. sst(1) mRNA was also expressed in the deep cerebellar nuclei [I-125]Tyr(3)-octreotide binding sites in cerebellar membranes correlated with recombinant sst(2), but not wi th sst(5) or sst(3) receptors and were found in the molecular layer of the cerebellum. [I-125]CGP 23996 (in Na+-buffer) binding in rat cereb ellum correlated with sst(1) or sst(4), but not with sst(2), sst(3) or sst(5) receptor binding. Similar data were obtained in rhesus monkey cerebellum. mRNAs for all five receptors were found in the granule cel l layer of the human cerebellum and/or in the dentate nucleus. [I-125] Tyr(3)-octreotide binding was strong in the molecular layer and correl ated with that of recombinant sst(2) receptors, but not with sst(3) or sst(5) receptors. [I-125]CGP 23996 (in Mg++-buffer) binding was heter ogeneous (about 75%. to sst(2) and 25% to sst(1) and/or sst(4) recepto rs). The molecular and granular layers were equally and the dentate nu cleus strongly labeled. Thus, SRIF receptors of the sst(2), sst(1) and /or sst(4) subtype are present in the rat, monkey and human cerebellum . In the latter two species, the sst(2) type appears to be predominant . Surprisingly, the high expression of sst(3) receptor mRNA is not sup ported by radioligand binding data in any of the species studied. The reason for this discrepancy remains to be elucidated.