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Abstract #6863 Published in IGR 4-1

Potentiation of sympathetic neurotransmission in bovine isolated irides by isoprostanes

Opere CA; Awe SO; Harris LC; Leday AM; Ohia SE
Free Radical Research 2001; 35: 257-264


Isoprostanes (IsoP) are formed by free radical catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. In the present study, the authors examined the effect of IsoP on norepinephrine (NE) release from the bovine isolated iris. Furthermore, they studied the role of IsoPs 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 F2α (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 μm) with an IC50 of 370 ± 50 nM. SQ 29548 (10 μm) also blocked the enhancement of electrically-evoked [3H]NE release induced by U46619 (10 μm) but not that caused by H2O2 (300 μm). The Tx synthetase inhibitor, carboxyheptylimidazole (10 μm) prevented the stimulatory effect of E2-IsoP on evoked [3H]NE release without affecting responses induced by H2O2. The authors conclude that IsoPs 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 IsoPs on NE release. However, endogenously generated IsoPs or Txs are not involved in H2O2-induced potentiation of sympathetic neurotransmission.

Dr. C.A. Opere, Department of Pharmaceutical and Administrative Sciences, School of Pharmacy and Allied Health Professions, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA


Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)



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