title: Lindane decreases forskolin-stimulated cyclic AMP accumulation but does not modify Gs in rat enterocytes.
abstract: Treatment of isolated rat enterocytes with the halogenated insecticide lindane (the gamma-isomer of hexachlorocyclohexane, HCCH) did not modify the general membrane fluidity (as estimated by a fluorescence polarization technique) nor the guanine nucleotide binding regulatory protein Gs (as studied by both ADP-ribosylation of its alpha subunit by cholera toxin and Gpp[NH]p stimulation of membrane adenylate cyclase activity). However, lindane decreased in a dose-dependent manner the effect of the diterpene forskolin on direct activation of the adenylate cyclase catalytic subunit. After 5 min of cell treatment with 0.5 mM lindane, the maximal stimulatory effect of forskolin (at 100 microM) decreased by about 50%. There was a certain degree of specificity since delta-HCCH was indeed more potent, whereas dieldrin and endrin (non-lindane related halogenated compounds) behaved as lindane, and alpha- and beta-HCCH were poorly efficient on the inhibition of forskolin stimulation of adenylate cyclase activity. A similar effect of lindane was observed on receptor-stimulated cyclic AMP accumulation by using vasoactive intestinal peptide instead of forskolin. The results on a non-receptor mediated effect of lindane on the adenylate cyclase catalytic subunit itself could be related to: (i) alterations of membrane microdomains surrounding this and other integral proteins which would result in modifications of their activities; and/or (ii) a reciprocal relation between the two main routes of signal transduction so that the activation of protein kinase C (or other Ca(2+)-dependent protein kinases) by lindane would lead to phosphorylation of the adenylate cyclase catalytic subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Carrero
authors.forename: N
authors.initials: N
authors.lastname: Rodríguez-Henche
authors.forename: L G
authors.initials: LG
authors.lastname: Guijarro
authors.forename: M N
authors.initials: MN
authors.lastname: Recio
authors.forename: M A
authors.initials: MA
authors.lastname: Pèrez-Albarsanz
authors.forename: J C
authors.initials: JC
authors.lastname: Prieto
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D010761:Phosphorus Radioisotopes; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: D008565:Membrane Proteins; D010703:Phorbol Esters; D010761:Phosphorus Radioisotopes; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; C008876:phorbol-12,13-didecanoate; D006165:Guanylyl Imidodiphosphate; D014660:Vasoactive Intestinal Peptide; D001556:Hexachlorocyclohexane; D002772:Cholera Toxin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine