Carboxy terminus of vasopressin required for activity but not binding.
Vasopressin antagonists are valuable pharmacological tools for investigating physiological and behavioural functions of the nonapeptide arginine-vasopressin (AVP). The removal of glycinamide from the carboxy terminus of AVP drastically reduces its characteristic vasopressor and antidiuretic activities. In contrast to this we show here that removal of the carboxy-terminal glycinamide or the glycine at position 9 from several vasopressin antagonists makes little difference to their ability to block vasopressor and antidiuretic responses to AVP. These data demonstrate the critical structural requirements of the carboxy-terminal position for receptor activation, in contrast to the lack of such requirements for receptor binding. They also provide an avenue to a wide variety of antagonists substituted at the carboxy terminus (for example radiolabelled derivatives and affinity ligands) and suggest clues for the development of more potent and/or selective antagonists.
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001681:Biological Assay; D004231:Diuresis / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014357:Trypsin; D014661:Vasoconstriction / Q000187:drug effects
D010446:Peptide Fragments; D001127:Arginine Vasopressin; D014357:Trypsin