A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps).
This paper describes the purification, sequence, and biological properties of a 38-amino acid residue peptide from the venom of Dendroaspis angusticeps which shared important sequence homologies with natriuretic peptides. Dendroaspis natriuretic peptide (DNP) relaxed aortic strips that had been contracted by 40 mM KCl with a potency (K0.5 = 20 nM) similar to that of atrial natriuretic peptide (ANP) and larger than that of C type natriuretic peptide (CNP). The relaxing actions of ANP and DNP (both at 100 nM) were mutually exclusive. Bovine aortic endothelial cells responded to ANP (K0.5 = 3 nM) and DNP (K0.5 = 3 nM) but not to CNP by a large activation of guanylate cyclase. Rat aortic myocytes showed larger cGMP responses to CNP (K0.5 = 10 nM) than to ANP or DNP (K0.5 = 100 nM). Finally, DNP completely prevented the specific 125I-ANP binding to clearance receptors in cultured aortic myocytes with a potency (Kd = 10 nM) that was less than that of ANP (Kd = 0.3 nM). It is concluded that DNP is a new member of the family of natriuretic peptides and that it recognizes ANPA receptors and clearance, ANPc receptors, but not CNP-specific ANPB receptors.
Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
H
H
Schweitz
P
P
Vigne
D
D
Moinier
C
C
Frelin
M
M
Lazdunski
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004546:Elapid Venoms / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D012911:Snakes
C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor