Effect of isoprostanes on sympathetic neurotransmission in the human isolated iris-ciliary body

Isoprostanes (IsoP's) are prostaglandin-like compounds that are derived from free-radical catalyzed peroxidation of arachidonic acid independent of the cyclcooxygenase enzyme. In the present study, we investigated the effect of IsoP's on norepinephrine (NE) release from human isolated iris-ciliary bodies. Isolated human iris-ciliary bodies were prepared for studies of [H-3]NE release using the superfusion method, Both 8-iso-prostaglandin F-2 alpha (F-2-IsoP) and the thromboxane (Tx) receptor agonist, U46619 enhanced field-stimulated [H-3]NE release from isolated, superfused human iris-ciliary bodies without affecting basal tritium efflux. On the other hand, an equimolar concentration (10 mu M) of 8-iso-prostaglandin E-2 (E-2-IsoP) inhibited evoked [H-3]NE overflow. The Tx-receptor antagonist, SQ 29548 blocked the enhancements of electrically-evoked [H-3]NE release induced by F-2-IsoP and U46619. However, the inhibitory responses elicited by E-2-IsoP was not antagonized by SQ 29548. We conclude that IsoP's can produce both excitatory and inhibitory effects on sympathetic neurotransmission in human isolated iris-ciliary bodies. The stimulatory effects of IsoP's on NE release may be mediated by Tx-receptors.