K depletion alters angiotensin II receptor expression in vascular smooth muscle cells.
Dietary K depletion (KD) results in increases in the number of angiotensin II (ANG II) receptors and prevents ANG II-induced downregulation of ANG II receptors in membrane preparations of vessels from KD animals. Because dietary KD results in changes in factors other than K, we K depleted vascular smooth muscle cells (VSMC) in culture to determine the specific effects of KD on ANG II receptor expression and processing. Scatchard analysis of ANG II uptake at 4 degrees C revealed that the number of surface receptors was increased by 37% in cells in which K had been reduced by 45%. This increase also occurred in the presence of cycloheximide. To determine the effect of KD on receptor processing, we measured the number of surface receptors after exposure to ANG II in concentrations sufficient to cause down-regulation. After 30-min exposure to ANG II, the number of surface receptors was reduced by 63% in control cells but only 33% in KD cells. Thirty minutes after withdrawing ANG II, surface binding returned to basal levels in control cells but was still reduced by 20% in KD cells. To determine the functional significance of impaired receptor processing, we measured ANG II uptake at 21 degrees C. Uptake at 21 degrees C depends on the functional number of receptors, i.e., the absolute number of surface receptors and the rate at which receptors are recycled to the surface after ANG II binding. ANG II uptake at 21 degrees C was reduced by 50% in KD cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Linas
S L
SL
Department of Medicine, University of Colorado Health Sciences Center, Denver 80204.
Marzec-Calvert
R
R
Ullian
M E
ME
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media; D015536:Down-Regulation / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000096:biosynthesis*
D003470:Culture Media; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D011188:Potassium