Neurosteroid modulation of [3H]flunitrazepam binding in the medulla: an autoradiographic study.
Neurosteroids bind to unique sites on the GABA(A) receptor complex and modulate receptor function. The effects of neurosteroids on GABA(A) receptors have been well characterized in forebrain regions. However, little is known about their effects on GABA(A) receptors in the medulla, especially those areas involved in autonomic reflex pathways. Stimulation of [3H]flunitrazepam binding to the GABA(A) receptor by two progesterone metabolites, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha-OH-DHP) and 3beta-hydroxy-5alpha-pregnan-20-one (3beta-OH-DHP), was studied using autoradiographic methods in the medulla and cerebellum of female rats at estrus. [3H]Flunitrazepam binding was enhanced by 3alpha-OH-DHP in every nucleus examined in the medulla and cerebellum. This effect was stereoselective since 3beta-OH-DHP had no effect on binding in any region. No differences were observed in the degree of stimulation of [3H]flunitrazepam binding by 3alpha-OH-DHP among medullary brain regions. However, in the cerebellum, the stimulation of binding was significantly greater in the granular layer than in the molecular layer. Stimulation of [3H]flunitrazepam binding by 3alpha-OH-DHP in nuclei involved in the baroreflex pathways supports previous studies which report that neurosteroids modulate autonomic regulation of blood pressure. These actions may also underlie alterations in autonomic function during pregnancy.
Garrett
K M
KM
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, USA. kennon-garrett@uokhsc.edu
Barron
K W
KW
Briscoe
R J
RJ
Heesch
C M
CM
D000818:Animals; D001345:Autoradiography; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism*; D018757:GABA Modulators / Q000494:pharmacology*; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D011280:Pregnanolone / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D014316:Tritium
D018757:GABA Modulators; D011963:Receptors, GABA-A; D014316:Tritium; D005445:Flunitrazepam; D011280:Pregnanolone