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 [3H]NE release using the superfusion method. Both 8-iso-prostaglandin F2alpha (F2-IsoP) and the thromboxane (Tx) receptor agonist, U46619 enhanced field-stimulated [3H]NE release from isolated, superfused human iris-ciliary bodies without affecting basal tritium efflux. On the other hand, an equimolar concentration (10 microM) of 8-iso-prostaglandin E2 (E2-IsoP) inhibited evoked [3H]NE overflow. The Tx-receptor antagonist, SQ 29548 blocked the enhancements of electrically-evoked [3H]NE release induced by F2-IsoP and U46619. However, the inhibitory responses elicited by E2-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.
Awe
S O
SO
Department of Pharmaceutical and Administrative Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA.
Opere
C A
CA
Harris
L C
LC
Uketui
A J
AJ
Ohia
S E
SE
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002924:Ciliary Body / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D004558:Electric Stimulation; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000819:agonists / Q000037:antagonists & inhibitors; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; 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; D009638:Norepinephrine