Structure-activity relationships of alpha-human atrial natriuretic peptide

The spasmolytic activity of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) and its related Peptides was determined in vitro using the chick rectum and the rat aorta. Natriuretic activity was also measured in the anesthetized rat, alpha-hANP-(7-28), with the NH2-terminal hexapeptide truncated, had greater spasmolytic and natriuretic effect than did alpha-hANP-(1-28). These responses were reduced by truncation of the COOH-terminal residues. alpha-hANP-(7-23), the cyclic structure of alpha-hANP-(1-28), exhibited weak aortic relaxation and natriuretic activities. However, alpha-hANP-(7-23) produced a greater relaxation than did alpha-hANP-(1-28) in the chick rectum. Elimination of Gly at position 9 reduced the spasmolytic and natriuretic activity. Substitution of amino acid residues at position 8, 12 and 13 changed these activities. Analogues containing the ethylene linkage instead of the disulphide bond had weak biological activity. These results indicate that the size of the 17-amino acid ring and the COOH-terminal residues of alpha-hANP are important for the expression of spasmolytic and natriuretic activity.