[I-125] TYR(10)-CORTISTATIN(14) LABELS ALL 5 SOMATOSTATIN RECEPTORS

The recently cloned rat preprocortistatin, which shows homology to the preprosomatostatin peptide, is thought to be enzymatically cleaved to cortistatin(14) (CST14) similarly to somatostatin(14) (SRIF14). High structural similarity of cortistatin(14) compared to SRIF14 suggested binding properties to somatostatin receptors similar to SRLF14. In the present study, we expressed stably the five human somatostatin recept or subtypes (hsst(1)-hsst(5)) in CCL39 cells (Chinese hamster lung fib roblast cells). The receptors were labelled with an iodinated analogue of CST14 ([I-125]Tyr(10)-cortistatin(14), [I-125]Tyr(10)-CST) to esta blish the pharmacological profile of hsst(1)-hsst(5) sites labelled wi th [I-125]Tyr(10)-CST. In parallel, [Leu(8),D-Trp(22),I-125-Tyr(25)]SR IF28 ([I-125]LTT-SRIF28) was used as a control at the five recombinant SRIF receptors stably expressed in CCL39 cells. High affinity [I-125] Tyr(10)-CST binding could be demonstrated to all five recombinant soma tostatin receptor subtypes. The pK(d) (-log mol/l) and B-max values (f mol/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 10.3 3+/-0.03, 5630+/-330, respectively. The pharmacological profiles deter mined with [I-125]Tyr(10)-CST and [I-125]LTT-SRIF28 were very similar at every receptor studied. These data suggest that cortistatin and som atostatin have similar high affinity for SRIF receptors. None of the r eceptors showed marked selectivity for either CST14/CST17 or the somat ostatins. In conclusion, the data show that cortistatin and somatostat in have very similar high affinity to all five recombinant somatostati n receptors. It remains to be seen whether there are specific receptor s which bind only somatostatins or cortistatins.