Endothelin-1, acting via the a receptor subtype, stimulates thymocyte proliferation in the rat

Abstract

Endothelins (ET s) are a family of vasoactive peptides widely distributed in the body systems, where they carry out major autocrine paracrine regulatory functions, acting through two main subtypes of receptors (ET a and ET b). Evidence suggests that ET s play a permissive role in the development of neural crest-derived craniofacial structures, among which the thymus. Therefore, we have investigated whether ET s regulate thymocyte proliferation in the adult rat ET-1 (which binds both ET a and ET b receptors) increased the mitotic index (% of metaphase-arrested cells) in the thymus cortex, while ET-3 (which preferentially binds ET b) and the selective ET b-receptor agonists BQ-3020 and IRL-1620 did not. The ET a-receptor antagonists BQ-123 and BQ-610, but not the ET b-receptor 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 endogenous ET s, through the activation of ET a receptors, are involved in the maintenance and stimulation thymocyte proliferation in the adult rat, thereby playing a possible important role in the modulation of the immune-system functions.