8-11-14-eicosatrienoic-acid and eicosa-8-11-14-trien-5-ynoic-acid

Enteric neural activity modulates active transepithelial ion transport in the intestine. We investigated the neural circuits mediating neurogenic secretion in mucosal explants from porcine ileum. Transmural electrical stimulation increased short-circuit current, a measure of active ion transport, by 35+/-2 microA/cm2. The neuronal Na+ channel blocker saxitoxin, the muscarinic cholinergic receptor antagonist atropine, the 5-hydroxytryptamine3 receptor antagonist tropisetron, and the cyclooxygenase inhibitor indomethacin inhibited this response. In addition, tropisetron inhibited the atropine-resistant portion of the response, and both atropine and indomethacin attenuated the saxitoxin-resistant component. Neurogenic secretion in porcine ileum appears to be mediated by tryptaminergic and prostanoid-sensitive cholinergic pathways.

Topics: 8,11,14-Eicosatrienoic Acid; Acetylcholine; Animals; Atropine; Electric Stimulation; Female; Ileum; In Vitro Techniques; Indoles; Indomethacin; Intestinal Mucosa; Ion Transport; Male; Prostaglandins; Saxitoxin; Serotonin; Serotonin Agents; Serotonin Antagonists; Swine; Tropisetron; Vasodilator Agents

8Z,11Z,14Z-Eicosatriene-5-ynoic acid and its tritium-labelled analogue, [5,6-3H]arachidonic acid, have been synthesized on the basis of acetylenic compounds. [5,6-3H]Arachidonic acid has been used as substrate for the enzymatic synthesis of [5,6-3H]PGE2 and [5,6-3H]PGF2 alpha.

Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acid; Arachidonic Acids; Chemical Phenomena; Chemistry; Dinoprost; Dinoprostone; Fatty Acids, Unsaturated; Prostaglandins E; Prostaglandins F

The quantitative relationships between the secretion of a granule-associated mediator, beta-hexosaminidase, and the oxidative metabolism of arachidonic acid by the 5-lipoxygenase pathway were analyzed for a homogeneous population of T cell-dependent, bone marrow-derived, murine mast cells. The mast cells were either sensitized with a monoclonal IgE and challenged with specific antigen, or to bypass a transmembrane signal, were stimulated with calcium ionophore A23187. The released products of the 5-lipoxygenase pathway were quantitated by integrated ultraviolet absorbance after resolution by reverse phase-high performance liquid chromatography in the case of 5-hydroxy-eicosatetraenoic acid (5-HETE), and by separate radioimmunoassays for leukotriene C4 (LTC4) and leukotriene B4 (LTB4). The activation-release response of the cells was perturbated by the introduction of three pharmacologic agents, each directed to different steps in the 5-lipoxygenase pathway of arachidonic acid metabolism, and the action of each agent was determined for separate cell samples while present and after its removal by washing. 5,6-Dehydroarachidonic acid (5,6-DHA), an irreversible inhibitor of 5-lipoxygenase, prevented formation of 5-HETE from exogenous [14C]arachidonic acid and from membrane-derived arachidonic acid in a dose-related fashion when sensitized mast cells, preincubated with drug, were washed before antigen activation. Release of 5-HETE, LTC4, and LTB4 was inhibited by 5,6-DHA in a corresponding dose-related fashion, with a minimal preincubation period of 1 to 5 min before the cells were washed and subjected to antigen-dependent activation. In contrast, the inhibitory effect of 5,6-DHA on beta-hexosaminidase release was lost after three washes and was not evident after one wash unless the preincubation period was extended to 15 min. The capacity of 5,6-DHA to prevent leukotriene generation without altering beta-hexosaminidase release was also observed with ionophore-activated mast cells. Preincubation of sensitized cells with diethylcarbamazine (DEC), followed by a wash before antigen-dependent activation, produced inhibition of leukotriene generation, no effect on beta-hexosaminidase release, and augmentation of 5-HETE release at the maximum dose studied; thus, DEC interrupts the pathway distal to the formation of 5-hydroperoxy-eicosatetraenoic acid (5-HPETE) from arachidonic acid by 5-lipoxygenase. Preincubation of sensitized cells with incremental amounts of the

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonate Lipoxygenases; Arachidonic Acids; beta-N-Acetylhexosaminidases; Bone Marrow Cells; Diethylcarbamazine; Hexosaminidases; Hydroxyeicosatetraenoic Acids; Immunoglobulin E; Leukotriene B4; Lipoxygenase; Lipoxygenase Inhibitors; Male; Mast Cells; Mice; Mice, Inbred BALB C; SRS-A

Topics: 8,11,14-Eicosatrienoic Acid; Cell Communication; Female; Humans; Indomethacin; Infant, Newborn; Leukocytes; Lymphocyte Activation; Maternal-Fetal Exchange; Pregnancy; Prostaglandins; T-Lymphocytes, Regulatory

[5,6-3H]arachidonic acid has been prepared by catalytic reduction of eicosa-cis-8,11,14-trien-5-ynoic acid (IV) over Lindlar catalyst. When either [5,6-3H]arachidonic acid or [5,6-3H]PGH2 is converted into PGI2 by swine aortic microsomes, the tritium at C-6 is lost to the medium. Thus, the progress of this enzymic rearrangement may be monitored by following the rate of tritium release. As swine aortic microsomes contain only low levels of cyclooxygenase, it is necessary to fortify the system with ram seminal vesicular microsomes (rich in cyclooxygenase) when [5,6-3H]arachidonic acid is used as the indirect substrate.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Aorta; Arachidonic Acids; Cytochrome P-450 Enzyme System; Epoprostenol; Intramolecular Oxidoreductases; Isotope Labeling; Kinetics; Magnetic Resonance Spectroscopy; Microsomes; Prostaglandins; Tritium