A new type of functional VIP receptor has an affinity for helodermin in human SUP-T1 lymphoblasts.
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.
Robberecht
P
P
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Waelbroeck
M
M
De Neef
P
P
Tastenoy
M
M
Gourlet
P
P
Cogniaux
J
J
Christophe
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008223:Lymphoma / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010451:Peptide PHI / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010451:Peptide PHI; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D006160:Guanosine Triphosphate; C040442:heliodermin; C043046:helospectin I; C043047:helospectin II; D000262:Adenylyl Cyclases