Sciatic nerve transection evokes lasting up-regulation of angiotensin AT2 and AT1 receptor mRNA in adult rat dorsal root ganglia and sciatic nerves.
The angiotensin AT2 receptor is involved in tissue repair and cellular stress responses in non-neuronal cells. We have previously observed that the AT2 receptor-induced neurite formation in PC12W cells is paralleled by a reduced neurofilament M expression as it occurs in nerve fiber regeneration. Here we show that transection and crush of sciatic nerve fibers of adult rats results in dramatic changes of AT2, AT1a and AT1b receptor mRNA in dorsal root ganglion neurons (DRGs) and in sciatic nerves 3, 14 and 28 days after axotomy and crush. The expression patterns were determined by reverse transcription polymerase chain reaction (RT-PCR) assay, and the specificity of amplification products was verified by Southern blot hybridization. Whereas axotomy evoked a transient increase of AT2 receptor mRNA by more than 1000% after 3 days in proximal and after 14 days in distal sciatic nerve stumps (510%), the maximum expression in DRGs was observed after 14 days (1100%). Sciatic nerve crush resulted in a time-dependent up-regulation of AT2 receptor mRNA in sciatic nerve segments coinciding with the successful regeneration of nerve fibers. In sciatic nerves, AT1a and AT1b receptor mRNA levels were increased within different time-courses and to different extents with a maximum expression of 570%. In contrast to AT1a receptor mRNAs, AT1b receptor mRNA levels were increased in DRGs by maximally 800%. These results suggest that AT2 and AT1 receptor-mediated pathways are involved in Schwann cell-mediated myelination and in neuroregenerative responses of DRGs.
Gallinat
S
S
Department of Pharmacology, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
Yu
M
M
Dorst
A
A
Unger
T
T
Herdegen
T
T
D000818:Animals; D017931:DNA Primers; D005727:Ganglia, Spinal / Q000737:chemistry / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D008297:Male; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D012584:Sciatic Nerve / Q000737:chemistry / Q000502:physiology / Q000601:surgery*; D015854:Up-Regulation / Q000502:physiology*
D017931:DNA Primers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin