Recovery of VIP/helodermin- and prostaglandin E1-stimulated adenylate cyclase activities in desensitized SUP-T1 human lymphoblasts.
VIP/helodermin receptors and PGE1 receptors coupled to adenylate cyclase underwent rapid homologous desensitization and/or down regulation in the human lymphoma SUP-T1 cell line: helodermin- and PGE1-stimulated adenylate cyclase activities in membranes decreased by 75% and 80%, respectively, after a 16-hr incubation of cells with 30 nM VIP or 0.1 microM PGE1. The adenylate cyclase response to helodermin doubled within 120 min of incubation with fresh medium, this part of the resensitization process being not significantly reduced by cycloheximide. The second slower phase of recovery attained 80% of control values after 8 hr and was significantly affected by cycloheximide added at time 0. These data were corroborated by our observations on [125I]helodermin binding to intact cells. In the case of functional PGE1 receptors, sixty percent of the adenylate cyclase response reappeared within 30-60 min, with the second phase of recovery leading, after 2-3 hr to 80-85% of control values of PGE1-stimulated enzyme activity. This resensitization process to PGE1 was, as a whole, cycloheximide sensitive.
Robberecht
P
P
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Brussels, Belgium.
De Neef
P
P
Abello
J
J
Damien
C
C
Coussaert
E
E
Christophe
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D010455:Peptides / Q000494:pharmacology*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; D011982:Receptors, Prostaglandin; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; C040442:heliodermin; D003513:Cycloheximide; D000262:Adenylyl Cyclases; D000527:Alprostadil