title: Modification of TSH-stimulated adenylate cyclase activity of bovine thyroid by manipulation of membrane phospholipid composition with a nonspecific lipid transfer protein.
abstract: The lipid composition of bovine thyroid plasma membranes was modified using the nonspecific lipid transfer protein from bovine liver. Incubation of plasma membranes with transfer protein and phosphatidylinositol-containing liposomes caused a strong, concentration dependent, inhibition of TSH-stimulated adenylate cyclase activity. Other phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidic acid were two to four times less effective as inhibitors of TSH-stimulation. The phosphatidylinositol-induced inhibition was not reversed when more than 80% of phosphatidylinositol incorporated was removed using phosphatidylinositol-specific phospholipase C. Incorporation of phosphatidylinositol in plasma membranes provoked no significant change in the fluorescence anisotropies of the fluorophores 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(14-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), indicating that the inhibition was not due to changes in membrane fluidity. At phosphatidylinositol concentrations causing a 66% reduction in TSH-stimulated adenylate cyclase activity cholera toxin- and forskolin-stimulated activity as well as basal activity were decreased by maximally 10%. Since TSH binding to bovine thyroid plasma membranes was not affected it is suggested that phosphatidylinositol can act as a negative modulator of the TSH activation of adenylate cyclase and this probably by interfering with the coupling between the occupied TSH receptor and the stimulatory GTP-binding regulatory protein of the adenylate cyclase complex.
authors.affiliation: RUCA-Laboratory for Human Biochemistry, University of Antwerp, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Depauw
authors.forename: M
authors.initials: M
authors.lastname: de Wolf
authors.forename: G
authors.initials: G
authors.lastname: van Dessel
authors.forename: H J
authors.initials: HJ
authors.lastname: Hilderson
authors.forename: A
authors.initials: A
authors.lastname: Lagrou
authors.forename: W
authors.initials: W
authors.lastname: Dierick
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000838:Anions; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D008081:Liposomes / Q000378:metabolism; D008099:Liver / Q000032:analysis; D008563:Membrane Lipids / Q000494:pharmacology / Q000502:physiology*; D010712:Phosphatidic Acids / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology / Q000502:physiology*; D013961:Thyroid Gland / Q000201:enzymology*; D013972:Thyrotropin / Q000494:pharmacology*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000838:Anions; D002352:Carrier Proteins; D008081:Liposomes; D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010743:Phospholipids; C030363:lipid transfer protein; D013972:Thyrotropin; D000262:Adenylyl Cyclases