Lindane effect upon the vasoactive intestinal peptide receptor/effector system in rat enterocytes.
Isolated rat enterocytes exposed to the insecticide lindane (the gamma-isomer of hexachlorocyclohexane, HCCH) showed an important decrease in the efficiency of the neuropeptide vasoactive intestinal peptide (VIP) upon the stimulation of cyclic AMP accumulation. The effect of lindane was time- and dose-dependent, optimal conditions being reached after 5 min incubation of cells at 25 degrees C with 0.5 mM of this organochlorine compound. Lindane action exhibited an important degree of specificity since the isomer alpha-HCCH and endrin reproduced the same inhibitory pattern but beta-HCCH and dieldrin were inactive. The inhibition of VIP-induced cyclic AMP accumulation could not be explained by a lindane-dependent reduction in the binding of VIP to its specific receptors. Among various possibilities, the results suggest the modification of membrane fluidity by lindane and/or the activation of Ca2+-dependent protein kinase C by this compound leading to phosphorylation of Gs/adenylate cyclase.
Carrero
I
I
Departmento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares-Madrid, Spain.
Fernández-Moreno
M D
MD
Pérez-Albarsanz
M A
MA
Prieto
J C
JC
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology
D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D001556:Hexachlorocyclohexane; D000242:Cyclic AMP