VIP and related peptides induce rapid homologous desensitization in the human lymphoma SUP T1 cell line
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P Robberecht1, P De Neef, M Waelbroeck
1Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Abstract:
Incubation of human SUP T1 lymphoblasts with VIP, helodermin and related peptides induced homologous desensitization within 5 min as indicated by: 1) a secondary decrease in cellular cyclic AMP levels, even in the presence of phosphodiesterase inhibitors, 2) a reduced capacity of cells to bind [125I]helodermin, 3) decreased helodermin stimulation of adenylate cyclase activity in membranes, and 4) unaffected NaF- and Gpp[NH]p-stimulated adenylate cyclase activities. The desensitizing ability of all peptides correlated with their efficacy to occupy cell receptors, except for [D-Phe2]VIP, a partial VIP agonist with low intrinsic activity, that did not desensitize.
Insights
Vasoactive intestinal peptide (VIP) and related peptides cause rapid homologous desensitization in lymphoblasts. This involves reduced cyclic AMP signaling and receptor binding, indicating a key cellular response to these signaling molecules.
Area of Science:
- Cellular signaling and molecular pharmacology
- Immunology and cell biology
Background:
- Vasoactive intestinal peptide (VIP) and related peptides are crucial signaling molecules.
- Understanding their cellular effects, including desensitization, is vital for pharmacology.
Purpose of the Study:
- To investigate the rapid homologous desensitization induced by VIP and related peptides in human lymphoblasts.
- To characterize the molecular mechanisms underlying this desensitization process.
Main Methods:
- Incubation of human SUP T1 lymphoblasts with VIP, helodermin, and analogs.
- Measurement of cellular cyclic AMP levels.
- Assessment of [125I]helodermin binding capacity.
- Evaluation of helodermin-stimulated adenylate cyclase activity in cell membranes.
- Analysis of NaF- and Gpp[NH]p-stimulated adenylate cyclase activities.
Main Results:
- Homologous desensitization occurred within 5 minutes of incubation.
- Desensitization manifested as decreased cyclic AMP levels, reduced helodermin binding, and diminished adenylate cyclase stimulation.
- NaF- and Gpp[NH]p-stimulated adenylate cyclase activities remained unaffected, suggesting a receptor-mediated process.
- Peptide desensitizing ability correlated with receptor occupancy, with [D-Phe2]VIP being an exception.
Conclusions:
- VIP and related peptides rapidly induce homologous desensitization in lymphoblasts.
- This desensitization involves multiple downstream signaling events and receptor interactions.
- The findings highlight the complex regulatory mechanisms of VIPergic signaling in immune cells.