title: Endothelin receptor expression in the normal and injured spinal cord: potential involvement in injury-induced ischemia and gliosis.
abstract: The endothelins (ETs) are a family of peptides that exert their biological effects via two distinct receptors, the endothelin A receptor (ET(A)R) and the endothelin B receptor (ET(B)R). To more clearly define the potential actions of ETs following spinal cord injury, we used immunohistochemistry and confocal microscopy to examine the protein expression of ET(A)R and ET(B)R in the normal and injured rat spinal cord. In the normal spinal cord, ET(A)R immunoreactivity (IR) is expressed by vascular smooth muscle cells and a subpopulation of primary afferent nerve fibers. ET(B)R-IR is expressed primarily by radial glia, a small population of gray and white matter astrocytes, ependymal cells, vascular endothelial cells, and to a lesser extent in smooth muscle cells. Fourteen days following compression injury to the spinal cord, there was a significant upregulation in both the immunoexpression and number of astrocytes expressing the ET(B)R in both gray and white matter and a near disappearance of ET(B)R-IR in ependymal cells and ET(A)R-IR in primary afferent fibers. Conversely, the vascular expression of ET(A)R and ET(B)R did not appear to change. As spinal cord injury has been shown to induce an immediate increase in plasma ET levels and a sustained increase in tissue ET levels, ETs would be expected to induce an initial marked vasoconstriction via activation of vascular ET(A)R/ET(B)R and then days later a glial hypertrophy via activation of the ET(B)R expressed by astrocytes. Strategies aimed at blocking vascular ET(A)R/ET(B)R and astrocyte ET(B)Rs following spinal cord injury may reduce the resulting ischemia and astrogliosis and in doing so increase neuronal survival, regeneration, and function.
authors.affiliation: Department of Preventive Science, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Peters
authors.forename: Scott D
authors.initials: SD
authors.lastname: Rogers
authors.forename: James D
authors.initials: JD
authors.lastname: Pomonis
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Egnaczyk
authors.forename: Cathy P
authors.initials: CP
authors.lastname: Keyser
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schmidt
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Ghilardi
authors.forename: John E
authors.initials: JE
authors.lastname: Maggio
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Mantyh
authors.forename: Greg F
authors.initials: GF
authors.lastname: Egnazyck
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005911:Gliosis / Q000209:etiology / Q000473:pathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000096:biosynthesis*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D020760:Spinal Cord Ischemia / Q000209:etiology / Q000473:pathology*
chemical_list: D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin