Agonist-dependent regulation of cloned human somatostatin receptor types 1-5 (hSSTR1-5): subtype selective internalization or upregulation.

Agonist regulation of somatostatin receptors (SSTRs) was investigated in stable CHO-K1 cells individually expressing the 5 human (h) SSTR subtypes. hSSTR 2,3,4, and 5 displayed rapid agonist-dependent internalization of [125I] LTT SST-28 ligand in a time- and temperature-dependent manner over 60 min. Maximum internalization of radioligand occurred with hSSTR3 (78%) followed by hSSTR5 (66%), hSSTR4 (29%) and hSSTR2 (20%). In contrast, hSSTR1 displayed virtually no internalization. Prolonged agonist treatment led to differential upregulation of some of the SSTRs. After 22 h, hSSTR1 was upregulated at the membrane by 110%, hSSTR2 and hSSTR4 by 26% and 22% respectively, whereas hSSTR3 and hSSTR5 showed little change. Agonist-induced recruitment of hSSTR1 to the membrane was confirmed by immunocytochemistry with hSSTR1 antibodies. These results show that SST regulates all 5 hSSTRs by differential subtype selective internalization or upregulation. Subtype selectivity for internalization and upregulation is inversely related.