Truncated atrial natriuretic peptide (ANP) analogs: relationship between receptor binding and cyclic GMP accumulation

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5429647

Scarborough, R; Schenk, D; Schwartz, K; Kang, L L; McEnroe, G; Arfsten, A; Lewicki, J

The authors have shown that cultured bovine aortic smooth muscle (BASM) cells contain high affinity receptor sites for the ANP, auriculin (ANP(4-28)). Furthermore, ANP(4-28) causes cyclic GMP (cGMP) levels to increase in BASM. In the present study, the authors synthesized a series of NH/sub 2/ and/or COOH truncated ANP(4-28) analogs and examined their ability to compete for /sup 125/I-ANP(4-28) binding to BASM and increase cGMP levels. ANP-mediated cGMP responses were reduced when amino acids were deleted from the NH/sub 2/ and/or COOH termini of ANP(4-28). Removal of the NH/sub 2/ terminal R, R-S, or R-S-S residues resulted in a 10X decrease in potency for cGMP stimulation. Deletion of the COOH terminal R-Y and F-R-Y residues resulted in a marked decline in potency. ANP's lacking the F-R-Y tripeptide were nearly inactive in stimulating cGMP accumulation. In contrast to the cGMP effects, NH/sub 2/ and/or COOH truncations of ANP(4-28) did not alter apparent receptor binding affinities (Ki(app)). All of these peptide analogs exhibited Ki(app)'s of 1-5 nM. Furthermore, peptides that bound effectively and failed to elicit cGMP responses did not antagonize ANP(4-28)-mediated cGMP increases. These binding and functional data suggest the presence of a single class of ANP receptors on BASM is insufficient to explain the actions of ANP's in these cells.

• Research Organization: California Biotechnology Inc., Mountain View
• OSTI ID: 5429647
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARBOXYLIC ACIDS
CATTLE
CELL CULTURES
CPB
DAYS LIVING RADIOISOTOPES
DOMESTIC ANIMALS
ELECTRON CAPTURE RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MUSCLES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RUMINANTS
TRACER TECHNIQUES
VERTEBRATES