vasoactive-intestinal-peptide-(10-28) and Lymphoma

The proliferation of human lymphoblastoma cell line (H9) was differently stimulated by Peptide Histidine Methionine (PHM) and Vasoactive Intestinal Peptide (VIP). PHM induced a cyclic AMP (cAMP) accumulation, abolished by Adenylate Cyclase (AC) inhibitors leading to a loss of proliferative effect. VIP mitogenic activity was Pertussis toxin (PTX) sensitive and AC inhibitors insensitive. Pharmacological experiments performed on H9 membranes with or without a GTP analogue indicated expression of both GTP-insensitive and -sensitive PHM/VIP high-affinity binding sites (HA). H9 cells expressed only the VPAC1 receptor. VIP(10-28), known as a VPAC1 antagonist, bond to all GTP-insensitive PHM sites and inhibited evenly the PHM and VIP mitogenic actions. These data strongly suggested different mechanisms initiated by VIP and PHM and highlighted the key role of GTP-insensitive binding sites in the control of cell proliferation.

Topics: Adenine; Adenylyl Cyclase Inhibitors; Analysis of Variance; Blotting, Southern; Bromodeoxyuridine; Cell Line, Tumor; Cell Proliferation; Cyclic AMP; Dose-Response Relationship, Drug; Drug Interactions; Gene Expression; Guanosine Triphosphate; Guanylyl Imidodiphosphate; Humans; Imines; Iodine Isotopes; Lymphoma; Peptide Fragments; Peptide PHI; Pertussis Toxin; Protein Binding; Radioligand Assay; Receptors, Cell Surface; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Vasoactive Intestinal Peptide