title: Predominant expression of type II vasoactive intestinal peptide receptors by human T lymphoblastoma cells: transduction of both Ca2+ and cyclic AMP signals.
abstract: 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.
authors.affiliation: Department of Medicine, University of California, San Francisco 94143-0711, USA.
authors.forename: M
authors.initials: M
authors.lastname: Xia
authors.forename: S P
authors.initials: SP
authors.lastname: Sreedharan
authors.forename: E J
authors.initials: EJ
authors.lastname: Goetzl
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D018005:Receptors, Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D002118:Calcium