AJP - Cell Physiology, Vol 257, Issue 4 C706-C713, Copyright © 1989 by American Physiological Society
Regulation of angiotensin II binding sites in neuronal cultures by catecholamines
L. M. Myers and C. Sumners
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610.
Previous studies determined that direct activation of protein kinase C
(PKC) with phorbol esters increases the number of angiotensin II (ANG
II)-specific binding sites in neuronal cultures prepared from the
hypothalamus and brain stem of 1-day-old rats. In the physiological
situation, PKC is activated by diacylglycerol, which can be produced by
multiple pathways, such as stimulation of inositol phospholipid (IP)
hydrolysis, phosphatidylcholine hydrolysis, or by de novo synthesis. In the
present study we have examined whether stimulation of IP hydrolysis, and
presumably activation of PKC, can mimic the actions of phorbol esters on
ANG II-specific binding. We have incubated neuronal cultures with agents
that increase IP hydrolysis and have determined the effects on ANG
II-specific binding. Incubation of neuronal cultures with norepinephrine
(NE) at concentrations (greater than 5 microM) and for times (15-60 min)
that cause large increases in IP hydrolysis caused increases in the number
of ANG II-specific binding sites, mimicking the actions of phorbol esters.
The return of IP hydrolysis to control values was associated with a return
of ANG II-specific binding to control levels. The upregulatory action of NE
was abolished by prazosin, demonstrating the involvement of alpha
1-adrenergic receptors. In addition, this effect was blunted by the PKC
antagonist H 7, suggesting PKC involvement in the response. Thus we have
determined a potential physiological mechanism by which stimulation of IP
hydrolysis by NE, and possible subsequent activation of PKC, leads to
upregulation of ANG II-specific binding sites in neuronal
cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
