Structure-activity relationships of atrial natriuretic factor (ANF). II. Effect of chain-length modifications on vascular reactivity.
The effect of the length of ANF peptides on the inhibition of the norepinephrine-induced contraction was studied. Starting from the 26 residues ANF (Arg101-Tyr126), shorter N- and/or C-terminal fragments were produced, either by N-terminal chemical cleavage or C-terminal enzymatic digestion of ANF or both respectively. The N-terminal removal of Arg101 did not modify the inhibitory response. Further N-terminal truncation up to des-Arg101-Arg102-Ser103-Ser104 ANF still produced a marked inhibitory effect on norepinephrine. In contrast C-terminal cleavage had a much more pronounced effect. Since des-Tyr126 ANF, des-Arg125-Tyr126 ANF and des-Phe124-Arg125-Tyr126 ANF exhibit much lower activities than the parent ANF. Finally, when the 5 residues C-terminal to Cys121 are removed, the resulting molecule is almost inactive. These data indicate that the C-terminal segment of ANF may modulate the binding of ANF to its receptor(s). Relatively, the N-terminal region seems to be much less important.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D045283:Natriuretic Agents; D009638:Norepinephrine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins / Q000032:analysis / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship
D045283:Natriuretic Agents; D010446:Peptide Fragments; D011506:Proteins; D009638:Norepinephrine