Vasoactive intestinal peptide and pituitary adenylate cyclase - Activating polypeptides (PACAP27 and PACAP38) protect CD4+CD8+ thymocytes from glucocorticoid-induced apoptosis

Abstract

In the present study, the effects of vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptides, PACAP27 and PACAP38, in a concentration range from 10-13 to 10-6 mol/L were studied in vitro on the spontaneous and dexamethasone (DEX)-induced apoptosis in rat thymocytes. The results show that VIP and both PACAPs inhibit significantly and in a similar way the DNA fragmentation characteristic of glucocorticoid-induced apoptosis and increase the cell survival of thymocytes, with a maximal effect observed at 10-8 to 10-9 mol/ L. This study showed the ability of the VIP-receptor (VIP-R) antagonist [N-Ac-Tyr1,D-Phe2]-GRF(1-29) amide to partially reverse the inhibitory effect of VIP and both PACAPs on DEX-induced apoptosis, providing evidence for a specific VIP1-R-mediated response and supporting the involvement of a single receptor for the three neuropeptides. Phenotypic analysis showed that VIP, PACAP27, and PACAP38 protect predominantly CD4+CD8+ thymocytes from glucocorticoid-induced apoptosis. These findings suggest that these neuropeptides could be involved in intrathymic T-cell maturation. © 1996 by The American Society of Hematology.