Endothelin immunoreactivity and mRNA expression in sensory and sympatheticneurones following selective denervation

The localization of endothelin (ET) in perivascular nerve varicosities supp orts pharmacological evidence that ET is a neurotransmitter in the autonomi c nervous system. To examine the potential source of ET previously localize d in cerebrovascular nerves, ganglia which send projections to these vessel s were immunolabelled for ET and examined at the ultrastructural level. The trigeminal (TG) and superior cervical ganglia (SCG) were examined in contr ol rats and following either sensory denervation or sympathectomy. In contr ol TC, ET immunolabelling was detected throughout the cytoplasm of a subpop ulation of neurones whereas in the SCG only the occasional ET-positive neur one was seen. Following sensory denervation with capsaicin, very few ET-imm unoreactive nerve cell bodies or nerve fibres were detected in the TG compa red with control ganglia, suggesting that ET is predominantly localized in primary afferent neurones, although some remaining myelinated nerve fibres stained positively. ET labelling of neurones in the SCG was unaffected by s ensory denervation. Following selective damage to sympathetic nerves with 6 -hydroxydopamine, there was a marked increase in intensity of ET-labelling of nerve fibres in the TG, probably due to increased availability of nerve growth factor for sensory nerves. There was no effect on ET immunoreactivit y in the nerve cell bodies and nerve fibres within the SCG. However, in sit u hybridization techniques demonstrated that 6-hydroxydopamine sympathectom y resulted in a marked increase in ET-1 mRNA expression in the SCG neurones . In conclusion, sensory nerves projecting from the TG are a more likely so urce of ET-positive perivascular nerves in cerebral arteries than sympathet ic nerves from the SCG. Damaged sympathetic neurones markedly increase ET m RNA expression. In view of the neuroprotective properties of ET, this may r epresent a compensatory mechanism to promote repair. (C) 2000 ISDN. Publish ed by Elsevier Science Ltd. All rights reserved.