title: Potentiation of sympathetic neurotransmission in bovine isolated irides by isoprostanes.
abstract: Isoprostanes (IsoP) are formed by free radical catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. In the present study, we examined the effect of IsoP on norepinephrine (NE) release from the bovine isolated iris. Furthermore, we studied the role of IsoP's in hydrogen peroxide (H2O2)-induced enhancement of NE release from this tissue. Isolated bovine irides were prepared for studies of [3H]NE release using the superfusion method. Release of [3H]NE was induced via electrical field stimulation. Both 8-iso-prostaglandin E2 (E2-IsoP) and 8-iso-prostaglandin F2 alpha (F2-IsoP) produced a concentration-related enhancement of field-stimulated [3H]NE release from isolated bovine irides, an effect that was mimicked by the thromboxane (Tx) receptor agonist, U46619 and by H2O2. The Tx-receptor antagonist, SQ 29548 inhibited responses to E2-IsoP (10 microM) with an IC50 of 370 +/- 50 nM. SQ 29548 (10 microM) also blocked the enhancement of electrically-evoked [3H]NE release induced by U46619 (10 microM) but not that caused by H2O2 (300 microM). The Tx synthetase inhibitor, carboxyheptylimidazole (10 microM) prevented the stimulatory effect of E2-IsoP on evoked [3H]NE release without affecting responses induced by H2O2. We conclude that IsoP's can enhance sympathetic neurotransmission in the bovine isolated iris, an effect that can be blocked by a Tx-receptor antagonist. Furthermore, endogenously produced Tx's mediate the stimulatory effect of IsoP's on NE release. However, endogenously generated IsoP's or Tx's are not involved in H2O2-induced potentiation of sympathetic neurotransmission.
authors.affiliation: Department of Pharmaceutical and Administrative Sciences, School of Pharmacy and Allied Health Professions, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Opere
authors.forename: S O
authors.initials: SO
authors.lastname: Awe
authors.forename: L C
authors.initials: LC
authors.lastname: Harris
authors.forename: A M
authors.initials: AM
authors.lastname: LeDay
authors.forename: S E
authors.initials: SE
authors.lastname: Ohia
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002417:Cattle; D015237:Dinoprost / Q000031:analogs & derivatives*; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D004558:Electric Stimulation; D028441:F2-Isoprostanes / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007498:Iris / Q000187:drug effects* / Q000294:innervation; D007536:Isomerism; D028421:Isoprostanes / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D017482:Receptors, Thromboxane / Q000819:agonists / Q000037:antagonists & inhibitors; D013564:Sympathetic Nervous System / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D028421:Isoprostanes; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015237:Dinoprost; D006861:Hydrogen Peroxide; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; C011987:8-isoprostaglandin E2; D009638:Norepinephrine