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, heloderm in, and secretin on VIP receptor number and affinity, as well as VIP-s timulated cyclic AMP production in rat peritoneal macrophages. Short-t erm (5-30 min) exposures of rat peritoneal macrophages to 0.1 mu M VIP induced a rapid reduction in specific binding. Pretreatment for 15 an d 30 min caused 26% (SEM = 6) and 48% (SEM = 4) reduction in specific binding, respectively. The maximal effect was observed at 120 min, cau sing a decrease of 67% (SEM = 6) in specific binding. Pretreatment wit h 0.1 mu M VIP for 15, 30, and 120 min caused 23% (SEM = 9), 52% (SEM = 4), and 76% (SEM = 4) reduction in cyclic AMP production, respective ly. Only VIP concentrations at the nanomolar level and higher were sho wn to be effective. The potency of VIP and related peptides to desensi tize was similar to their potency to occupy receptors and to activate cyclic AMP production. The internalization of radioiodinated VIP was a lso studied. It was shown that receptor-bound ligand is internalized d uring the downregulation process. However, the diminution in VIP bindi ng to macrophages was not completely explained by internalization.