ENDOTHELIN-1, ACTING VIA THE A-RECEPTOR SUBTYPE, STIMULATES THYMOCYTEPROLIFERATION IN THE RAT

Endothelins (ETs) are a family of vasoactive peptides widely distribut ed in the body systems, where they carry out major autocrine/paracrine regulatory functions, acting through two main subtypes of receptors ( ETA and ETB) Evidence suggests that ETs play a permissive role in the development of neural crest-derived craniofacial structures, among whi ch the thymus. Therefore, we have investigated whether ETs regulate th ymocyte proliferation in the adult rat ET-1 (which binds both ETA and ETB receptors) increased the mitotic index (% of metaphase-arrested ce lls) in the thymus cortex, while ET-3 (which preferentially binds ETB) and the selective ETB-receptor agonists BQ-3020 and IRL-1620 did not. The ETA-receptor antagonists BQ-123 and BQ-610, but not the ETB-recep tor antagonist BQ-788, abolished the ET-1 effect. Moreover, BQ-123 and BQ-610, when administered alone, evoked a significant decrease in the mitotic index. Collectively, these findings clearly indicate that end ogenous ETs, through the activation of ETA receptors, are involved in the maintenance and stimulation thymocyte proliferation in the adult r at, thereby playing a possible important role in the modulation of the immune-system functions.