Regulation of uveal sympathetic neurotransmission by peroxides.
OBJECTIVE
To investigate the effect of naturally occurring and synthetic peroxides on norepinephrine release from isolated iris-ciliary bodies of several mammalian species.


METHODS
Hemiirides (bovine) and iris-ciliary bodies (human, rabbit, and rat) were incubated in Krebs solution containing [3H]-norepinephrine ([3H]NE) for 60 minutes. After incubation, tissues were set up for studies of [3H]NE release using the superfusion method. Release of [3H]NE was elicited through electrical field stimulation.


RESULTS
In bovine irides, hydrogen peroxide (H2O2), cumene hydroperoxide (cuOOH), and tert-butyl hydroperoxide (buOOH) caused a concentration-dependent potentiation of field-stimulated [3H]NE release with the following rank order of potency: cuOOH > H2O2 > buOOH. Furthermore, the free radical scavenger, melatonin (2 mM), prevented the enhancement of evoked [3H]NE overflow elicited by H2O2 and cuOOH. At equimolar concentrations, H2O2 (1 mM) increased stimulated [3H]NE release from rabbit, human (mean age, 29.7; range, 15 to 48 years), and Fischer 344 rat (4 months old) iris-ciliary bodies by 98%, 50%, and 40%, respectively. However, H2O2 (1 mM) caused a 9% increase in evoked [3H]NE release in tissue from aged Fischer 344 rats (30 months old) and a 5% decrease in neurotransmitter release in tissue from old human donors (mean age, 72.3 years; range, 69 to 74 years).


CONCLUSIONS
Peroxides such as H2O2 can potentiate sympathetic neurotransmission in the anterior uvea of several mammalian species. In bovine irides, H2O2-induced enhancement of neurotransmitter release can be mimicked by synthetic peroxides and may involve the generation of reactive oxygen species.
Opere
C
C
Department of Pharmaceutical and Administrative Sciences, Creignton University Health Sciences Center, Omaha, Nebraska 68178, USA.
Tang
L
L
Imler
M
M
Kim
J
J
Okoye
M
M
Ohia
S
S
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D002417:Cattle; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007498:Iris / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D010545:Peroxides / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D014602:Uvea / Q000187:drug effects / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D016166:Free Radical Scavengers; D010545:Peroxides; D008550:Melatonin; D009638:Norepinephrine