Recently, an
ANF-sensitive
guanylate cyclase (GC-A) has been cloned from a rat brain cDNA library. Here we studied the stimulation of
cyclic GMP accumulation in response to
atrial natriuretic factor (
ANF),
urodilatin and
atriopeptin I (AP-1) in a rat
glioma C6 cell line permanently transfected with GC-A as well as GC-A activity in membranes from these C6 cells and in membranes from COS-7 cells that were transiently transfected with GC-A. We also measured binding affinities for these
natriuretic peptides in the membrane preparations. These characteristics of GC-A were compared to those of membrane preparations from adrenal cortex of bovine and human origin. The order of potency of stimulation of
cyclic GMP accumulation in permanently transfected
glioma cells was
ANF greater than
urodilatin greater than AP I; AP I stimulated
cyclic GMP accumulation. A similar order of potency was obtained for stimulation of
guanylate cyclase activity in membranes from permanently transfected
glioma cells as well as from transiently transfected COS-7 cells. In contrast,
AP-1 was uneffective to stimulate
guanylate cyclase in membrane preparations from adrenal cortex from bovine as well as from human origin. Furthermore,
urodilatin was equipotent to
ANF in these preparations. Binding affinities were comparable for
ANF and
urodilatin in membranes from cells transfected with GC-A and in membranes from adrenal cortex of both sources, whereas
AP-1 had a weaker affinity in all preparations studied.(ABSTRACT TRUNCATED AT 250 WORDS)