vasoactive-intestinal-peptide and Leukemia--Radiation-Induced

1. Based on radioligand binding and adenylate cyclase activation, functional receptors to vasoactive intestinal peptide(VIP)/helodermin, were shown to coexist with beta 2-adrenoceptors and prostaglandin receptors in membranes from a cultured cloned BL/VL3 cell line of murine T-cell lymphoma induced by a radiation leukemia virus. 2. The relative potency of VIP-related peptides to stimulate adenylate cyclase activity was: helodermin greater than VIP greater than peptide histidine isoleucinamide. Five VIP analogs inhibited 125I-iodo-VIP binding and stimulated adenylate cyclase activity, their decreasing order of potency being: VIP greater than [D-Asp3]VIP greater than [D-Ser2]VIP greater than [D-Ala4]VIP = [D-His1]VIP = [D-Phe2]VIP. [D-Phe2]VIP acted as a partial agonist (with an intrinsic activity of 0.1 as compared to that of VIP = 1.0) and competitively inhibited helodermin- and VIP-stimulated adenylate cyclase activity with a similar Ki (0.07-0.10 microM). These data suggest the existence, in this murine T-cell lymphoma, of VIP receptors of the 'helodermin-preferring' subtype that are coupled to adenylate cyclase.

Topics: Adenylyl Cyclases; Alprostadil; Animals; Catecholamines; Cell Membrane; Enzyme Activation; Intercellular Signaling Peptides and Proteins; Leukemia, Radiation-Induced; Lymphoma; Mice; Peptide PHI; Peptides; Receptors, Adrenergic, beta; Receptors, Gastrointestinal Hormone; Receptors, Prostaglandin; Receptors, Vasoactive Intestinal Peptide; Retroviridae; T-Lymphocytes; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

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