Homologous regulation of vasoactive intestinal peptide (VIP) receptors on rat peritoneal macrophages.
In the present study, we examined the effect of pretreatment with VIP and various peptides structurally related to VIP such us PHI, helodermin, and secretin on VIP receptor number and affinity, as well as VIP-stimulated cyclic AMP production in rat peritoneal macrophages. Short-term (5-30 min) exposures of rat peritoneal macrophages to 0.1 microM VIP induced a rapid reduction in specific binding. Pretreatment for 15 and 30 min caused 26% (SEM = 6) and 48% (SEM = 4) reduction in specific binding, respectively. The maximal effect was observed at 120 min, causing a decrease of 67% (SEM = 6) in specific binding. Pretreatment with 0.1 microM VIP for 15, 30, and 120 min caused 23% (SEM = 9), 52% (SEM = 4), and 76% (SEM = 4) reduction in cyclic AMP production, respectively. Only VIP concentrations at the nanomolar level and higher were shown to be effective. The potency of VIP and related peptides to desensitize was similar to their potency to occupy receptors and to activate cyclic AMP production. The internalization of radioiodinated VIP was also studied. It was shown that receptor-bound ligand is internalized during the downregulation process. However, the diminution in VIP binding to macrophages was not completely explained by internalization.
Pozo
D
D
Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Spain.
Guerrero
J M
JM
Calvo
J R
JR
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007328:Insulin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D010451:Peptide PHI / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism*; D012633:Secretin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D010451:Peptide PHI; D010455:Peptides; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; C040442:heliodermin; D000242:Cyclic AMP