Regulation of neurotransmitter release from ocular tissues by isoprostanes

Abstract

Isoprostanes are prostaglandin-like compounds formed in vivo primarily by free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. In addition to being utilized as reliable indicators of oxidative stress, 8-isoprostanes exert pharmacological actions on smooth muscles from several tissues and organs, and they play a role in the release of neurotransmitters from the central and peripheral nervous systems. In the anterior uvea of the eye, 8-isoprostanes produce both excitatory and inhibitory effects on sympathetic neurotransmission in isolated mammalian iris ciliary bodies. Thromboxane (TP) receptors mediate the stimulatory action of isoprostanes on norepinephrine (NE) release from sympathetic nerves. In bovine retina, the 8-isoprostanes exhibit a biphasic regulatory effect on potassium-induced [3H]-D-aspartate release, with low concentrations being inhibitory and high concentrations causing an excitatory effect. Excitatory effects of 8-isoprostanes are mediated by TP receptors, while inhibitory responses are mediated by prostaglandin E (EP) receptors. The 8-isoprostanes produce pharmacological actions on sympathetic neurotransmission in mammalian anterior uvea, a response that is species-dependent. In the posterior segment of the eye, 8-isoprostanes elicit a complex response on the retina involving the activation of both prostanoid TP and EP receptors. An effect of isoprostanes on neurotransmitter pools provides new pharmacological target sites for the therapy of some ocular diseases.