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Structure‐activity studies on endothelin (16–21), the C‐terminal hexapeptide of the endothelins, in the guinea‐pig bronchus
Author(s) -
Rovero Paolo,
Patacchini Riccardo,
Maggi Carlo Alberto
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12119.x
Subject(s) - endothelins , guinea pig , endothelin receptor , bronchus , terminal (telecommunication) , endocrinology , medicine , endothelin 1 , peptide , chemistry , anatomy , biology , receptor , biochemistry , respiratory disease , computer science , lung , telecommunications
1 We describe the results of a structure‐activity study in which the C‐terminal hexapeptide of the endothelins, endothelin (16–21), is compared with shorter fragments; hexapeptides bearing amino‐acid substitutions and the corresponding C‐terminal fragments of sarafotoxins. The guinea‐pig bronchus was used in this study since it is the most sensitive preparation for endothelin (16–21) thus far developed. 2 The biological results obtained with endothelin (16–21) and analogues demonstrate that the contractile activity of the C‐terminal hexapeptide of endothelin on the guinea‐pig bronchus depends on quite close structural requirements, strongly suggestive of a receptor interaction. The following features appear to be essential for the biological activity: (a) the C‐terminal free carboxylic function; (b) the L‐configuration of Trp‐21; (c) the β‐carboxylic function of Asp‐18; (d) the presence of Leu‐17 and (e) the imidazole moiety of His‐16. 3 The hexapeptide corresponding to the C‐terminal portion of sarafotoxin, sarafotoxin (16–21), was devoid of biological activity. This behaviour might be related to the proposed existence of more than one receptor for the endothelin/sarafotoxin family in the guinea‐pig bronchus.