PHARMACOLOGICAL CHARACTERIZATION OF SOMATOSTATIN RECEPTORS IN RAT CEREBELLAR NUCLEI

Rat cerebellar nuclei contain somatotropin release-inhibiting factor (SRIF) receptors that bind [I-125][Leu(8),D-Trp(22) Tyr(25)]SRIF-28 but do not bind [I-125][Tyr(0),D-Trp(8)]SRIF-14. The aim of the present study was to investigate the pharmacological profile of these receptors by means of binding experiments on tissue sections and quantitative autoradiography. Competition experiments indicated the presence of a single class of [I-125][Leu(8),D-Trp(22),Tyr(25)]SRIF-28 binding sites in the lateral cerebellar nuclei, showing similar affinities for SRIF-14 and SRIF-28, but low affinity for short-chained analogs. The IC50 values for somatostatin analogs to compete with the binding of [I-125][Leu(8),D-Trp(22),Tyr(25)]SRIF-28 in the lateral cerebellar nuclei ranked as follows: [Leu(8),D-Trp(22),Tyr(25)]SRIF-28 similar to SRIF-14 similar to SRIF-28 < CGP 23996 < D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2, (BIM 23052) < SMS 201-995 similar to N-Ahep-(7-10)SRIF-14-Bzl < < MK 678 < D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2 (BIM 2305 6) < D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]Nal-NH2 (NC 8-12). Optimum binding of [I-125][Leu(8),D-Trp(22),Tyr(25)]SRIF-28 did not require divalent cations, and was partly inhibited by guanosine 5' triphosphate. It appears from this study that the rat lateral cerebellar nuclei contain a pure population of receptors exhibiting the same binding characteristics as the recently cloned sstr1 somatostatin receptor. These nuclei could thus provide a useful model in which to investigate the characteristics of native sstr1.