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1 Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC, USA; Department of Physiology, University of Occupational and Environmental Health, Kitakyushu, Japan
2 Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu, Japan
3 Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC, USA
4 Department of Physiology, University of Occupational and Environmental Health, Kitakyushu, Japan
5 Department of Physiology, University of Occupational and Environmental Health, Kitakyushu, Japan; Kyushu Nutrition Welfare University, Kitakyushu, Japan
* To whom correspondence should be addressed. E-mail: bkis{at}wfubmc.edu.
Prostaglandins produced in cerebral endothelial cells (CECs) are the final signal transduction mediators from the periphery to the brain during fever response. However, prostaglandins are organic anions at physiological pH and they enter cells poorly using simple diffusion. Several transporters have been described which specifically transport prostaglandins across cell membranes. We examined the expression of the two principal prostaglandin carriers, prostaglandin transporter (PGT) and multidrug resistance associated protein 4 (MRP4) in cells of the blood-brain barrier and in choroid epithelial cells in vitro as well as in vivo in rat brain in control conditions and following LPS challenge. We detected PGT in primary cultures of rat CECs, astrocytes, pericytes and choroid epithelial cells. LPS stimulation had no effect on the expression level of PGT in these cells; however, after LPS stimulation the polarized, dominantly luminal expression pattern of PGT significantly changed. MRP4 is also expressed in CECs and its level was not influenced by LPS treatment. In rat brain PGT was highly expressed in the supraoptic and paraventricular nuclei of the hypothalamus, in the ependymal cell layer of the third ventricle and in the choroid plexus. LPS treatment increased the expression of PGT in the supraoptic and paraventricular nuclei. Our results suggest that PGT and MRP4 likely play a role in transporting prostaglandins through the blood-brain and blood-cerebrospinal fluid barriers and may be involved in the maintenance of prostaglandin homeostasis in the brain and in the initiation of fever response.
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