Glucocorticoids upregulate the high affinity receptors for vasoactive intestinal peptide (VIP) on human mononuclear leucocytes in vitro.
Glucocorticoids were shown to induce a time- and dose-dependent increment of specific [125I]VIP-binding on human mononuclear leucocytes in culture. Cortisol (0.5 microM) increased specific [125I]VIP-binding to 132% of control after 48 h preincubation, to 162% after 96 h, and to 175% after 144 h. Dexamethasone (0.5 microM) increased specific [125I]VIP-binding to 140%, 194% and 210% after the same time periods. Analysis of the binding data revealed an increase in Bmax to 119% by cortisol (0.5 microM, 48 h) and to 194% by dexamethasone (0.5 microM, 48 h), and no change in Kd for the high affinity receptor after preincubation. The number of low affinity binding sites for VIP was also increased by glucocorticoids. However, in contrast to the high affinity receptor, low affinity binding sites were initially downregulated in culture, and glucocorticoids induced a restitution to number and affinity close to those obtained for freshly isolated leucocytes. This increase in low affinity binding sites was blocked by actinomycin D, in contrast to the high affinity receptor upregulation which was independent of de novo protein synthesis. Furthermore, corresponding to the glucocorticoid induced high affinity receptor upregulation, an increase in VIP stimulated cyclic AMP production was observed. The results of this study suggest that leucocyte responsiveness to VIP can be influenced by glucocorticoids.
Wiik
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Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller.
D000242:Cyclic AMP / Q000096:biosynthesis; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D011500:Protein Synthesis Inhibitors; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D003609:Dactinomycin; D014660:Vasoactive Intestinal Peptide; D003907:Dexamethasone; D000242:Cyclic AMP; D006854:Hydrocortisone