title: Regulations of astrocytic functions by endothelins: roles in the pathophysiological responses of damaged brains.
abstract: The receptors for endothelins (ETs) are classified into the ET(A) and ET(B) types. ET(B) receptors are highly expressed in astrocytes, but pharmacological usages of this receptor are not clarified. In this article, recent studies on the pathophysiological roles of astrocytic ET(B) receptors in the brain are reviewed. The administration of ET(B) agonists and antagonists in nerve injury models showed that several astrocytic functions are regulated by ET(B) receptors. The activation of ET(B) receptors causes morphological alterations and proliferation of cultured astrocytes. Astrocytes produce various bio-active substances that can affect damage to nerve tissues. ETs stimulate the production of neurotrophic factors by astrocytes. This action improves impaired brain functions. On the other hand, the production of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF), which induce brain edema, also are stimulated by ETs. These findings indicate that astrocytic functions are effectively regulated by modulations of ET(B) receptors. In brain insults and neurodegenerative diseases, these functions of astrocytes affect the protection and repair of damaged nerve tissues. Thus, astrocytic ET(B) receptors could be a target for novel types of neuroprotective drugs.
authors.affiliation: Laboratory of Pharmacology, Osaka Ohtani University, Osaka, Japan. koyamay@osaka-ohtani.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Koyama
authors.forename: Shotaro
authors.initials: S
authors.lastname: Michinaga
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D016232:Endothelins / Q000819:agonists / Q000502:physiology*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D044023:Receptor, Endothelin B / Q000819:agonists / Q000502:physiology*
chemical_list: D016232:Endothelins; D018696:Neuroprotective Agents; D044023:Receptor, Endothelin B