Receptor-induced degradation of atrial natriuretic peptide by a rabbit carotid artery smooth muscle cell.
We have used a smooth muscle cell line isolated from rabbit carotid artery (RCA) as a model system with which to study the expression of atrial natriuretic peptide (ANP) receptors and, in addition, the receptor-mediated degradation of ANP. RCA cells bind rat alpha ANP-(1-28) reversibly at 37 C, apparently to a single class of high affinity (Kd approximately equal to 50 pM) binding sites (approximately equal to 20,000 sites per cell). Binding of rat alpha ANP-(1-28) elicits rapid accumulation of intracellular cGMP. However, the concentrations of rat alpha ANP-(1-28) and related peptides, abbreviated at the N- and C-terminals, required to stimulate cGMP synthesis are substantially greater than those required for binding. Analysis by HPLC of 125I-labeled rat alpha ANP-(1-28) bound to RCA cells at 37 C illustrates the rapid and continuous degradation of the radioiodinated rat alpha ANP-(1-28) to two radiolabeled products, one of which, 125I-labeled tyrosine is the major radiolabeled component that dissociates from the cells. Measurement of rat alpha ANP-(1-28) interaction with RCA cells by radioligand binding techniques therefore subsumes several processes. One of these processes is the rapid and continuous degradation of specifically bound ANP by these cells and perhaps also other target cells that respond to ANP.
Hughes
R J
RJ
Department of Medicine, University of California, San Diego, La Jolla 92093.
Struthers
R S
RS
Fong
A M
AM
Insel
P A
PA
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002339:Carotid Arteries / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000502:physiology*
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor