Biochemical studies of rat atrial natriuretic factor.
The natriuretic substances were purified from rat atrium (ANF, atrial natriuretic factor) and were shown to be identical with the inhibitor of norepinephrine-induced contraction of smooth muscle. Their four native forms were isolated. Amino acid sequence analyses showed they are peptides with 35, 31, 30 and 25 amino acid residues respectively and contain a ring structure consisting of 17 amino acid residues and a disulfide bridge. The presence of a high molecular weight prohormone was shown. cDNA coding for the precursor was cloned and used to deduce the amino acid sequence of the preprohormone. Genomic DNA for ANF was cloned and the presence of two introns were found. Several ANF peptides were synthesized. Structure-function studies showed that the ring structure is essential for the activity. Antibodies produced against the synthetic 25 amino acid residue ANF were used to develop radioimmunoassay. The presence of ANF in rat plasma was demonstrated as evidence that ANF is a circulating hormone. ANF was also found in the hypothalamus of rats. The quantitative determination of the synthetic ability of ANF has been determined by the application of ANF cDNA for the quantification of ANF messenger RNA. Immunohistochemical methods localized ANF in cardiac atriocytes, gonadotrophs in anterior pituitary and adrenal medulla (chromaffin cells). A strong immuno-reactivity was found in dark cells of the collecting ducts of the kidney. ANF increases cyclic GMP in target cells suggesting that cyclic GMP may be the intracellular mediator of ANF action.
Inagami
T
T
Misono
K S
KS
Grammer
R T
RT
Fukumi
H
H
Maki
M
M
Tanaka
I
I
McKenzie
J C
JC
Takayanagi
R
R
Pandey
K N
KN
Parmentier
M
M
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor; D001483:Base Sequence; D002417:Cattle; D002850:Chromatography, Gel; D006152:Cyclic GMP / Q000378:metabolism; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology; D009124:Muscle Proteins / Q000032:analysis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011487:Protein Conformation; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D014664:Vasodilation / Q000187:drug effects
D009124:Muscle Proteins; C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor; D004247:DNA; D006152:Cyclic GMP