[125I]Tyr10-cortistatin14 labels all five somatostatin receptors

Abstract

The recently cloned rat preprocortistatin, which shows homology to the preprosomatostatin peptide, is thought to be enzymatically cleaved to cortistatin₁₄ (CST₁₄) similarly to somatostatin₁₄ (SRIF₁₄). High structural similarity of cortistatin₁₄ compared to SRIF₁₄ suggested binding properties to somatostatin receptors similar to SRIF₁₄. In the present study, we expressed stably the five human somatostatin receptor subtypes (hsst₁–hsst₅) in CCL39 cells (Chinese hamster lung fibroblast cells). The receptors were labelled with an iodinated analogue of CST₁₄ ([¹²⁵I]Tyr¹⁰-cortistatin₁₄, [¹²⁵I]Tyr¹⁰-CST) to establish the pharmacological profile of hsst₁–hsst₅ sites labelled with [¹²⁵I]Tyr¹⁰-CST. In parallel, [Leu⁸,D-Trp²²,¹²⁵I-Tyr²⁵]-SRIF₂₈ ([¹²⁵I]LTT-SRIF₂₈) was used as a control at the five recombinant SRIF receptors stably expressed in CCL39 cells. High affinity [¹²⁵I]Tyr¹⁰-CST binding could be demonstrated to all five recombinant somatostatin receptor subtypes. The pK_d (–log mol/l) and B_max values (fmol/mg) for hsst_1–5 receptors were: 10.02±0.04, 220±30; 9.45±0.09, 340±70; 10.06±0.11, 340±50; 9.67±0.14, 340±110 and 10.33±0.03, 5630±330, respectively. The pharmacological profiles determined with [¹²⁵I]Tyr¹⁰-CST and [¹²⁵I]LTT-SRIF₂₈ were very similar at every receptor studied. These data suggest that cortistatin and somatostatin have similar high affinity for SRIF receptors. None of the receptors showed marked selectivity for either CST₁₄/CST₁₇ or the somatostatins. In conclusion, the data show that cortistatin and somatostatin have very similar high affinity to all five recombinant somatostatin receptors. It remains to be seen whether there are specific receptors which bind only somatostatins or cortistatins.