PHARMACOLOGICAL CHARACTERIZATION OF HUMAN CEREBRAL-CORTEX SOMATOSTATIN SRIF(1) AND SRIF(2) RECEPTORS

Radioligand binding studies were performed in membranes of human cereb ral cortex using [I-125]Tyr(3)-octreotide in the presence of 5 mM MgCl 2, [I-125]SRIF-14 ([I-125]Tyr(11)-SRIF-14) and [I-125]CGP 23996 25]c[A su-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) both in the presence of 1 20 mM NaCl, to characterise the nature oi the somatostatin (SRIF) rece ptors. The pharmacological profile of human brain SRIF recognition sit es was compared with that of recombinant human SRIF(1) (sst(2)-sst(3)- sst(?)5) or SRIF(2) receptors (sst(1)-sst(4)) and with that of native rat sst(1), sst(2) and sst(4) receptors. [I-125]Tyr(3)-octreotide labe lled binding sites in human cerebral cortex: B-max = 238 +/- 36 fmol/m g protein and pK(d) = 9.73 +/- 0.08. The pharmacological profile of [I -125]Tyr(3)-octreotide labelled sites correlated very significantly wi th that of recombinant human sst(2) receptors (r = 0.98) and much less with those of recombinant human sst(3) (r = 0.65) or sst(5) receptors (r = 0.72). The correlation between [I-125]Tyr(3)-octreotide binding to native sst(2) receptors in human and rat cerebral cortex was also h ighly significant (r = 0.97). [I-125]SRIF-14 and [I-125]CGP 23996 bind ing (performed in the presence of 120 mM NaCl) in the human cerebral c ortex identified very similar populations of sites B-max = 44 +/- 7 an d 36 +/- 5 fmol/mg protein and pK(d) = 9.44 +/- 0.08 and 9.48 +/- 0.10 , respectively. The pharmacological Profiles of the sites labelled wit h [I-125]SRIF-14 and [I-125]CGP 23996 correlated highly significantly with those of recombinant human sst(1) (r = 0.97-0.99) or sst(4) recep tors (r = 0.91-0.94). Similarly, the correlations between [I-125]SRIF- 14 or [I-125]CGP 23996 binding in human cortex and [I-125]SRIF-14 bind ing to native sst(1) sites in rat cerebral cortex were also highly sig nificant (r = 0.97 and 0.94, respectively). Finally, the pharmacologic al profile of native rat lung sst4 sites determined with [I-125]LTT-SR IF-28 ([Leu(8),D-Trp(22) I-125-Tyr(25)]SRIF-28) correlated with [I-125 ]SRIF-14 and [I-125]CGP 23996 binding in human cortex; r = 0.91 and 0. 87, respectively. The present data show that in human cerebral cortex, [I-125]Tyr(3)-octreotide labels SRIF(1) receptor sites which are best characterised as of the sst(2) type, whereas [I-125]SRIF-14 and [(II) -I-125]CGP 23996 (both in the presence of 120 mM NaCl), label sites wh ich fit almost equally well with sst(1) or sst(4) receptors and theref ore are best described as of the SRIF(2) type. Under the conditions us ed, there was no evidence that either of these ligands would label sst (3) or sst(5) receptors in human cerebral cortex.