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.

Arachidonic acid metabolites and chloride secretion in rabbit distal colonic mucosa.

CAMUSSI, Giovanni;GIORDANO, Carlo;
1991-01-01

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.
261
G443
450
Calderaro V; Giovane A; De Simone B; Camussi G; Rossiello R; Quagliuolo L; Servillo L; Taccone W; Giordano C; Balestrieri C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/104650
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