Predominant expression of type II vasoactive intestinal peptide receptors by human T lymphoblastoma cells: transduction of both Ca2+ and cyclic AMP signals

J Clin Immunol. 1996 Jan;16(1):21-30. doi: 10.1007/BF01540969.


An immunoregulatory role for vasoactive intestinal peptide (VIP) is suggested by the high concentrations in subsets of neurons supplying lymphoid organs and by the capacity of VIP to affect T lymphocyte functions. The Tsup-1 line of human T lymphoblastoma cells expresses both type I and type II G protein-coupled VIP receptors (Rs), as shown by detection of the encoding mRNAs with reverse transcription-polymerase chain reaction analyses. Northern blot quantification of the relative amounts 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 125I-VIP to 8.95 x 10(4) high-affinity sites/cell (Kd = 6.0 nM) and 7.45 x 10(5) low-affinity sites/cell (Kd = 210 nM). VIP increased [cAMP]i in Tsup-1 cells (EC50 = 14.4 nM) and stimulated a rapid and transient increase in [Ca2+]i (EC50 = 30 nM). Functional coupling of G proteins to type II VIPRs was suggested by the change in binding of 125I-VIP to Tsup-1 cell membranes from two sites with Kd values of 3.8 and 109 nM to one site of Kd 30 nM by GTP-gamma-S and the suppression by pertussis toxin of increases in [Ca2+]i evoked by VIP. The VIP antagonists, VIP4-28 and (4-Cl-D-Phe6-Leu17) VIP, inhibited 125I-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites / immunology
  • Calcium / metabolism*
  • Cyclic AMP / biosynthesis
  • Cyclic AMP / metabolism*
  • Humans
  • Molecular Sequence Data
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Receptors, Vasoactive Intestinal Peptide / biosynthesis*
  • Receptors, Vasoactive Intestinal Peptide / genetics
  • Receptors, Vasoactive Intestinal Peptide / physiology
  • Signal Transduction / immunology*
  • Tumor Cells, Cultured


  • Receptors, Vasoactive Intestinal Peptide
  • Cyclic AMP
  • Calcium