PREDOMINANT EXPRESSION OF TYPE-II VASOACTIVE-INTESTINAL-PEPTIDE RECEPTORS BY HUMAN T-LYMPHOBLASTOMA CELLS - TRANSDUCTION OF BOTH CA2-AMP SIGNALS( AND CYCLIC)

An immunoregulatory role for vasoactive intestinal peptide (VIP) is su ggested by the high concentrations in subsets of neurons supplying lym phoid organs and by the capacity of VIP to affect T lymphocyte functio ns. The Tsup-1 line of human T lymphoblastoma cells expresses both typ e I and type II G protein-coupled VTP receptors (Rs), as shown by dete ction of the encoding mRNAs with reverse transcription-polymerase chai n reaction analyses. Northern blot quantification of the relative amou nts of mRNA encoding the two VIPRs in Tsup-1 cells indicated that type II predominates over type I, as it does in human blood CD4(+) T cells . Tsup-1 cells bound I-125-VIP to 8.95 X 10(4) high-affinity sites/cel l (K-d = 6.0 nM) and 7.45 x 10(5) low-affinity sites/cell (K-d = 210 n M). VIP increased [cAMP](i) in Tsup-1 cells (EC(50) = 14.4 nM) and sti mulated a rapid and transient increase in [Ca2+](i) (EC(50) = 30 nM). Functional coupling of G proteins to type II VIPRs was suggested by th e change in binding of I-125-V1P to Tsup-1 cell membranes from two sit es with K-d values of 3.8 and 109 nM to one site of K-d 30 nM by GTP-g amma-S and the suppression by pertussis toxin of increases in [Ca2+](i ) evoked by VIP. The VIP antagonists, VIP4-28, and (4-Cl-D-Phe(6)-Leu( 17)) VIP, inhibited I-125-VIP binding by type II VIPRs, as well as VIP -elicited increases in [Ca2+](i) and [cAMP](i). Type II VIPRs thus are the major transducers of VIP signals to a subset of human T cells.