ABSTRACT
The transport of lysophospholipids through the rat blood-retina and blood-brain barrier was determined by using radioactive 1-palmitoyl-2-lysophosphatidylcholine (Pam-lysoPtdCho) and by measuring the uptake of this labeled compound into the retina and various brain regions after short in situ carotid perfusion. The transport was not affected by probenecid (0.25 mM), but it was inhibited, in a dose-dependent manner, by circulating albumin which is able to bind tightly to lysophosphatidylcholine and lowered the availability of the latter for tissue extraction. Radiotracer transfer in the retina was higher than in brain regions. The permeability-surface area products (PS) changed with the inclusion of unlabeled Pam-lysoPtdCho, showing that transport across retinal and brain microvessels is mainly saturable. The data provided an estimate of transport constants (Vmax, Km and non-saturable constant Kd). However, we could not distinguish whether this saturable process represents the saturation of a transport carrier or simple passive diffusion followed by the saturation of enzymatic reactions. In brain tissue lipid extract, 20 s after carotid injection, radiolabel was associated by 45% to unmetabolized Pam-lysoPtdCho. Partial acylation to phosphatidylcholine, as well as hydrolysis and redistribution of the fatty acyl moiety into main phospholipid classes also occurred. The present results, compared to our previous data, indicate that PamlysoPtdCho is transported faster and/or in greater amounts than unesterified fatty acids.
Subject(s)
Blood-Brain Barrier/physiology , Capillary Permeability/physiology , Eye/blood supply , Lysophosphatidylcholines/pharmacokinetics , Retina/physiology , Animals , Biological Transport , Carotid Arteries , Male , Microcirculation/physiology , Perfusion , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
The blood-retina and blood-brain transport of fatty acids was studied in control and lipid hydroperoxide-treated rats by measuring the permeability-surface area product (PS) to [1-14C]palmitate. An in situ carotid perfusion method was used. PS values were evaluated: (1) just after intracarotid injection of hydroperoxides; or (2) after a short-term systemic treatment for 1 week with sonicated emulsion of phospholipids-linoleate peroxidized mixture. Compared with saline-treated rats, PS remarkably decreased in the retina and most brain regions studied after acute, arterial injection of hydroperoxide preparations. On the contrary, the transport index significantly increased in the retina and almost all the brain areas after 7 days i.v. treatment with hydroperoxide emulsion. It is suggested that hydroperoxides acutely administered before transport radiotracer brought about a reinforcement of microvasculature junctional area or hampered substrate diffusion across endothelial membrane. On the other hand, upon short-term i.v. administration, hydroperoxides presumably triggered a lipid structure derangement of endothelial cell membranes and zonulae occludens due to their local accumulation and/or high capability of generating oxygen-free radicals.
Subject(s)
Blood-Brain Barrier/drug effects , Blood-Retinal Barrier/drug effects , Lipid Peroxides/pharmacology , Palmitates/metabolism , Animals , Brain/drug effects , Brain/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Fatty Acids, Unsaturated/metabolism , Rats , Rats, Sprague-Dawley , Retina/drug effects , Retina/metabolismABSTRACT
The permeability-surface area product (PS) of [1-14C]docosahexaenoate and [1-14C]palmitate at the blood-retina (BRB) and blood-brain barrier (BBB) was determined after in situ brain perfusion in Sprague-Dawley rats. The intracarotid injection procedure involved continuous infusion of albumin-bound fatty acids for up to 20 s. In the retina, and visual, parietal and frontal cortex, there was a significant decrease in mean PSs for docosahexaenoate compared to the palmitate group. For optic nerve and tract, superior colliculus, lateral geniculate, striatum, hippocampus and olfactory bulb, the comparison of PS values between the two fatty acid-injected groups of animals did not reveal any difference. It is suggested that the lower docosahexaenoate transport, compared to 16:0, across microvascular endothelium of the retina and other cortical regions might help explain the highest availability and selective retention of the essential 22:6(n-3) fatty acid in these nervous system structures.
