Pharmacological characterisation of human cerebral cortex somatostatin SRIF1 and SRIF2 receptors

Radioligand binding studies were performed in membranes of human cerebral cortex using [¹²⁵I]Tyr³-octreotide in the presence of 5 mM MgCl₂, [¹²⁵I]SRIF-14 ([¹²⁵I]Tyr¹¹-SRIF-14) and [¹²⁵I]CGP 23996 ([¹²⁵I]c[Asu-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) both in the presence of 120 mM NaCl, to characterise the nature of the somatostatin (SRIF) receptors. The pharmacological profile of human brain SRIF recognition sites was compared with that of recombinant human SRIF₁ (sst₂-sst₃-sst₅) or SRIF₂ receptors (sst₁-sst₄) and with that of native rat sst₁, sst₂ and sst₄ receptors. [¹²⁵I]Tyr³-octreotide labelled binding sites in human cerebral cortex: B _max = 238 ± 36 fmol/mg protein and pK_d = 9.73 ± 0.08. The pharmacological profile of [¹²⁵I]Tyr³-octreotide labelled sites correlated very significantly with that of recombinant human sst₂ receptors (r = 0.98) and much less with those of recombinant human sst₃ (r = 0.65) or sst₅ receptors (r = 0.72). The correlation between [¹²⁵I]Tyr³-octreotide binding to native sst₂ receptors in human and rat cerebral cortex was also highly significant (r = 0.97). [¹²⁵I]SRIF-14 and [¹²⁵I]CGP 23996 binding (performed in the presence of 120 mM NaCl) in the human cerebral cortex identified very similar populations of sites B _max = 44 ± 7 and 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 with [¹²⁵I]SRIF-14 and [¹²⁵I]CGP 23996 correlated highly significantly with those of recombinant human sst₁ (r = 0.97–0.99) or sst₄ receptors (r = 0.91–0.94). Similarly, the correlations between [¹²⁵I]SRIF-14 or [¹²⁵I]CGP 23996 binding in human cortex and [¹²⁵I]SRIF-14 binding to native sst₁ sites in rat cerebral cortex were also highly significant (r = 0.97 and 0.94, respectively). Finally, the pharmacological profile of native rat lung sst₄ sites determined with [¹²⁵I]LTT-SRIF-28 ([Leu⁸,D-Trp²²,¹²⁵I-Tyr²⁵]SRIF-28) correlated with [¹²⁵I]SRIF-14 and [¹²⁵I]CGP 23996 binding in human cortex; r = 0.91 and 0.87, respectively. The present data show that in human cerebral cortex, [¹²⁵I]Tyr³-octreotide labels SRIF₁ receptor sites which are best characterised as of the sst₂ type, whereas [¹²⁵I]SRIF-14 and [¹²⁵I]CGP 23996 (both in the presence of 120 mM NaCl), label sites which fit almost equally well with sst₁ or sst₄ receptors and therefore are best described as of the SRIF₂ type. Under the conditions used, there was no evidence that either of these ligands would label sst₃ or sst₅ receptors in human cerebral cortex. Received: 8 August 1996 / Accepted: 8 November 1996