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-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.
Delgado
M
M
Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad Complutense, Madrid, Spain.
Garrido
E
E
Martinez
C
C
Leceta
J
J
Gomariz
R P
RP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D004249:DNA Damage; D003864:Depression, Chemical; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; D015704:CD4 Antigens; D016827:CD8 Antigens; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D003907:Dexamethasone