J. Biol. Chem., Vol. 263, Issue 26, 13199-13202, 09, 1988
Regulation of atrial natriuretic factor receptors by angiotensin II in rat vascular smooth muscle cells
PE Chabrier, P Roubert, MO Lonchampt, P Plas and P Braquet
Institut Henri Beaufour Research Laboratories, Les Ulis, France.
Atrial natriuretic factor (ANF) is actively involved in the control of
blood pressure and fluid homeostasis as a physiological antagonist of the
renin-angiotensin system. To evaluate a possible interaction between ANF
and angiotensin II (Ang-II) receptors, we investigated the effect of long
term pretreatment (18 h) of rat cultured vascular smooth muscle cells with
Ang-II. Binding of 125I-labeled ANF and cyclic GMP production induced by
ANF were measured. After preincubation of the cells with Ang-II (1, 10, and
100 nM), the number of ANF binding sites (Bmax) was decreased by 30, 59,
and 71%, respectively, with a slight decrease of the Kd values.
Sar1-Ile8-Ang-II (100 nM), a specific Ang-II receptor antagonist, totally
inhibited the down-regulation induced by Ang-II (10 nM). Moreover, the
regulatory effect of Ang-II on ANF receptors appeared more slowly as
compared to ANF homologous receptor regulation. Ang-II pretreatment did not
desensitize but increased cyclic GMP production elicited by ANF, implying
that only the number of non-guanylate cyclase-coupled receptors was
affected. These findings, which were not observed with 100 nM of
epinephrine, norepinephrine, histamine, serotonin, and Arg-vasopressin,
demonstrate a specific and functional link between ANF and Ang-II
receptors. This study also shows that the regulation of ANF receptors is
heterogeneous, providing new evidence of multiple classes of ANF receptors.
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