The two subtype 1 somatostatin receptors of rainbow trout, Tsst _1A and Tsst_1B, possess both distinct and overlapping ligand binding and agonist-induced regulation features

In the present study, two isoforms of somatostatin receptor subtype one, previously obtained from the brain of rainbow trout, Tsst_1A and Tsst_1B, were stably transfected in the Chinese hamster ovary cell line (CHO-K1) and their binding properties were characterized. High affinity binding of somatostatin by expressed receptors was saturable and ligand selective. Both Tsst_1A and Tsst_1B preferentially bound peptides derived from preprosomatostatin I (PPSS I; e.g., SS-14-I) over those derived from PPSS II (containing Tyr⁷, Gly¹⁰-SS-14-I at their C-terminus; e.g., SS-25-II). The rank order of ligand affinities for Tsst_1A was SS-28-I>SS-14-I>SS-26-I≫SS-28-II>SS-14- II>SS-25-II. The rank order for Tsst_1B was SS-14-I>SS-28- I>SS-26-1≫SS-28-II>SS-25-II>SS-14-II. Agonist-induced regulation of Tsst_1A and Tsst_1B was also investigated. After 30 min of SS-14-I exposure, both Tsst_1A and Tsst_1B underwent rapid internalization; ca. 60% of membrane Tsst_1A was internalized and only about 40% of membrane Tsst_1B was internalized. Prolonged agonist exposure (up to 48 h) induced up-regulation of membrane-expressed Tsst _1A, but had no effect on Tsst_1B. These results indicate that Tsst1s display both distinct and overlapping ligand binding and agonist-induced regulation features. Such features may form the basis of ligand-selection and have important consequences on target organ responsiveness.