title: Arachidonic acid metabolites and chloride secretion in rabbit distal colonic mucosa.
abstract: The relationships between arachidonic acid (AA) metabolism and chloride secretion were investigated in mucosal preparations of rabbit distal colon. Tissues displayed a significant cyclooxygenase activity already in nonstimulated conditions and incubation with exogenous AA and calcium ionophore A23187 produced a predominant prostaglandin F2 alpha (PGF2 alpha) profile [PGF2 alpha greater than PGE2 greater than thromboxane B2 (TxB2) greater than 6-keto-PGF1 alpha] as assessed by HPLC of tissue homogenates, whereas 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) was not detected in AA- or A23187-stimulated tissues. Radioimmunological assays showed that PGE2 synthesis was time dependent, plateaued at 10 min, and proceeded at rates 15-20 times over TxB2 and 6-keto-PGF1 alpha. Among the PGs produced by colonic mucosa, only PGE2 and, to a lower extent, PGF2 alpha were found to stimulate chloride secretion and cAMP synthesis. Pretreatment with 10 microM 5,8,11,14-eicosatetraynoic acid, a cyclo- and lipoxygenase inhibitor, prevented AA-induced chloride secretion and PG and cAMP synthesis with the same strength as the cyclooxygenase inhibitor indomethacin. No effects were found after preincubation with nordihydroguaiaretic acid, a lipoxygenase blocker with moderate cyclooxygenase inhibitory properties, and caffeic acid, a lipoxygenase inhibitor. 5-HETE (5 microM) had no effect on short-circuit currents (Isc) and chloride transport, but it significantly reduced the increase in Isc, chloride secretion, and PGE2 synthesis elicited by AA or A23187. Platelet-activating factor, reported to stimulate rabbit colon Isc through an indomethacin-sensitive pathway, was not detected at concentrations as low as 10(-10) M.
authors.affiliation: Department of Biochemistry and Biophysics, University of Naples, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Calderaro
authors.forename: A
authors.initials: A
authors.lastname: Giovane
authors.forename: B
authors.initials: B
authors.lastname: De Simone
authors.forename: G
authors.initials: G
authors.lastname: Camussi
authors.forename: R
authors.initials: R
authors.lastname: Rossiello
authors.forename: L
authors.initials: L
authors.lastname: Quagliuolo
authors.forename: L
authors.initials: L
authors.lastname: Servillo
authors.forename: W
authors.initials: W
authors.lastname: Taccone
authors.forename: C
authors.initials: C
authors.lastname: Giordano
authors.forename: C
authors.initials: C
authors.lastname: Balestrieri
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon; D000242:Cyclic AMP / Q000378:metabolism; D004594:Electrophysiology / Q000379:methods; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D002712:Chlorides; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D015117:5,8,11,14-Eicosatetraynoic Acid; D000001:Calcimycin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D012964:Sodium; D000242:Cyclic AMP; D007213:Indomethacin