Endothelin-converting enzymes and endothelin receptor B messenger RNAs areexpressed in different neural cell species and these messenger rnas are coordinately induced in neurons and astrocytes respectively following nerve injury

There is some evidence that endothelins may be a signal mediator between ne uronal and glial cells, at least in some regions of the brain. To evaluate this possibility, the localization of messenger RNAs for endothelin-convert ing enzymes and endothelin receptor B in the rat brain were examined using ill situ hybridization histochemistry. The messenger RNAs for endothelin-co nverting enzyme-1 and endothelin-converting enzyme-2 were expressed mainly in neurons located in various brain regions, whereas the messenger RNA for endothelin receptor B was mainly localized in the astrocytes located throug hout the brainstem, Bergmann glia, choroid plexus and ependymal cells. The localization patterns of endothelin-converting enzyme and endothelin recept or B messenger RNAs were strikingly different. For instance, in the cerebel lum, endothelin-converting enzyme-1 messenger RNA was localized in Purkinje cells, and endothelin-converting enzyme-2 mRNA was expressed in Purkinje c ells and granule cells. On the other hand, endothelin receptor B messenger RNA was expressed in Bergmann glia and the astrocytes located in the granul e cell layer. This suggests that final cleavages of big endothelins are per formed on neuronal cells, and the major target of the processed endothelins could be astrocytes, which express endothelin receptor B most abundantly i n the brain. Since evidence that endothelin is implicated in brain injury h as also accumulated, we examined whether the expressions of endothelin-conv erting enzymes and endothelin receptor B are regulated by nerve injury. Fol lowing hypoglossal nerve injury, expression of messenger RNA for endothelin -converting enzymes-1 and -2 and endothelin receptor B was enhanced in the injured motor neurons and astrocytes respectively. The up-regulation of the se messenger RNAs was also confirmed by a reverse transcription-polymerase chain reaction based strategy. These results lead us to suggest that endothelin can be an inducible interc ellular mediator between injured neurons and astrocytes in response to nerv e injury. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights rese rved.