Chemical lesion of the inferior olive reduces [125I]sarcosine1-angiotensin II binding to AT2 receptors in the cerebellar cortex of young rats.
In young rats, AT2 receptors and AT2 receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus. We previously detected AT2 receptor binding, but not AT2 receptor mRNA, in the molecular layer of the cerebellar cortex. To determine whether AT2 receptors are expressed in climbing fiber terminals which arise to the molecular layer from the inferior olive and innervate Purkinje cells, we chemically destroyed olivary neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin 3-acetylpyridine. Lesions of the inferior olive reduced [125I]Sar1-Ang II binding to AT2 receptors and AT2 receptor mRNA levels in this area by 50%, and produced a similar decrease in AT2 receptor binding in the molecular layer of the cerebellar cortex. The extent of binding reduction was similar 3 days and 7 days after the lesion. 3-Acetylpyridine lesions did not change [125I]Sar1-Ang II binding to AT1 receptors in the molecular layer of the cerebellar cortex or AT1 receptor mRNA levels in Purkinje cells. AT2 receptor binding and AT2 receptor mRNA levels in the deep cerebellar nuclei were also not affected by 3-acetylpyridine. Our results support the hypothesis that AT2 receptors are produced by inferior olivary neurons and transported through climbing fibers to the molecular layer of the cerebellar cortex. The high expression of AT2 receptors in the inferior olivary-cerebellar pathway during a crucial time in postnatal development of climbing fiber-Purkinje cell connectivity suggest a role of AT2 receptors in the development of this pathway.
Jöhren
O
O
Section on Pharmacology, National Institute of Mental Health, 10 Center Drive MSC 1514, Building 10, Room 2D-57, Bethesda, MD 20892, USA. johreno@irp.nimh.nih.gov
Häuser
W
W
Saavedra
J M
JM
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism*; D000818:Animals; D002525:Cerebellar Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D009847:Olivary Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*
D007457:Iodine Radioisotopes; D011725:Pyridines; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; C010835:3-acetylpyridine; D015059:1-Sarcosine-8-Isoleucine Angiotensin II