helospectin-i and Lymphoma

1. Functional vasoactive intestinal peptide (VIP)/helodermin receptors and beta 2-adrenoceptors coexist in membranes from a cultured cloned BL/VL3 cell line of murine T-cell lymphoma induced by a radiation leukemia virus (see preceding paper in this journal). 2. Short-term (5-30 min) exposures of BL/VL3 cells to VIP or isoproterenol induced both homologous and heterologous desensitization. The potency of VIP and isoproterenol to desensitize was similar to their potency to occupy receptors and activate adenylate cyclase. 3. Long-term (16-h) exposure of BL/VL3 cells to VIP induced homologous down regulation only, whereas isoproterenol induced both homologous and heterologous down regulation. The potency of VIP, peptide histidine isoleucinamide, helodermin, helospectin, and [D-Phe2]VIP on the one hand, and of isoproterenol on the other hand, to decrease homologous responses was comparable to their potency for receptor occupancy and adenylate cyclase activation.

Topics: Adenylyl Cyclases; Animals; Cell Membrane; Drug Tolerance; Enzyme Activation; Guanylyl Imidodiphosphate; Intercellular Signaling Peptides and Proteins; Isoproterenol; Leukemia, Radiation-Induced; Lymphoma; Mice; Peptide PHI; Peptides; Receptors, Adrenergic, beta; Retroviridae; Sodium Fluoride; T-Lymphocytes; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

A new type of VIP receptor was characterized in human SUP-T1 lymphoblasts. The order of potency of unlabeled peptides, in the presence of [125I]helodermin, was: helodermin(1-35)-NH2 = helodermin(1-27)-NH2 greater than helospectin greater than VIP = PHI greater than [D-Ser2]VIP greater than [D-Asp3]VIP greater than [D-His1]VIP greater than or equal to [D-Ala4]VIP greater than or equal to secretin = GRF. This specificity was distinct from that of all VIP receptors described so far in that: (i) the affinity for helodermin (Kd = 3 nM) was higher than that of VIP (Kd = 15 nM) and PHI (Kd = 20 nM); and (ii) position 4 played an important role in ligand binding. The labeled sites were likely to be functional receptors as adenylate cyclase in crude lymphoblastic membranes (200-10,000 x g pellets) was stimulated by peptides, in the presence of GTP, with the following order of potency: helodermin(1-35)-NH2 greater than helodermin(1-27)-NH2 greater than helospectin = VIP = PHI.

Topics: Adenylyl Cyclases; Cell Membrane; Guanosine Triphosphate; Humans; Intercellular Signaling Peptides and Proteins; Kinetics; Lymphoma; Peptide Fragments; Peptide PHI; Peptides; Receptors, Gastrointestinal Hormone; Receptors, Vasoactive Intestinal Peptide; T-Lymphocytes; Tumor Cells, Cultured; Vasoactive Intestinal Peptide