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 s tudy was to investigate the pharmacological profile of these receptors by means of binding experiments on tissue sections and quantitative a utoradiography. Competition experiments indicated the presence of a si ngle class of [I-125][Leu(8),D-Trp(22),Tyr(25)]SRIF-28 binding sites i n the lateral cerebellar nuclei, showing similar affinities for SRIF-1 4 and SRIF-28, but low affinity for short-chained analogs. The IC50 va lues for somatostatin analogs to compete with the binding of [I-125][L eu(8),D-Trp(22),Tyr(25)]SRIF-28 in the lateral cerebellar nuclei ranke d as follows: [Leu(8),D-Trp(22),Tyr(25)]SRIF-28 similar to SRIF-14 sim ilar 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-12 5][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 popu lation 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.