Lack of cross talk between alpha1-adrenergic and angiotensin type 1 receptors in neurons of spontaneously hypertensive rat brain.
Norepinephrine causes downregulation of angiotensin II (Ang II) receptors in Wistar-Kyoto rat (WKY) brain neuronal cultures. The aim of this study was to compare the cross talk between Ang II and alpha1-adrenergic receptors in these neuronal cultures. Norepinephrine causes a 66 percent decrease in Bmax of Ang II type 1 (AT1) receptors in neuronal cultures of WKY brain. This decrease is mediated by the interaction of norepinephrine with the alpha1a-adrenergic receptor subtype. Norepinephrine also causes a decrease in mRNA levels for AT1 receptors. A maximal decrease of 83 percent in AT1, receptor mRNA is observed in 8 hours with 100 micromol/L norepinephrine, is blocked by 5-methyluradipil, and involves inhibition of AT1 receptor transcription. Furthermore, decreases in the AT1 receptor and its mRNA are associated with a significant attenuation of AT1 receptor-mediated stimulation of norepinephrine transporter mRNA in WKY brain neurons. In contrast, norepinephrine does not decrease AT1 receptors or mRNA and has no effect on Ang II stimulation of norepinephrine transporter mRNA in neuronal cultures of spontaneously hypertensive rat brain. Thus, these data show that norepinephrine-mediated downregulation of AT1 receptors is associated with a parallel decrease in AT1 mRNA and Ang II stimulation of norepinephrine transporter mRNA and involves the alpha1a-adrenergic receptor in neurons of WKY brain. This cross talk between the two receptors is lacking in neurons of spontaneously hypertensive rat brain.
Yang
H
H
Department of Physiology, University of Florida, College of Medicine, Gainesville 32610, USA.
Lu
D
D
Raizada
M K
MK
D000818:Animals; D001483:Base Sequence; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013045:Species Specificity
D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D011945:Receptors, Angiotensin; D009638:Norepinephrine