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

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-Tyr(1),D-Phe(2)]-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. (C) 1996 by The American Society of Hematology.