Skip to main content

MOLECULAR AND PHARMACOLOGICAL CHARACTERIZATION OF KININ RELATED PEPTIDES

Objective


The existence of a kallikrein kinin system has been shown in the eel (Anguilla anguilla), and the active kinin purified and sequenced. Some predicted analogues of eel bradykinin have been synthesized. On the basis of the biological activity, the previously unidentified residue appeared to be tryptophan.

The metabolism of bradykinin has been examined in selected tissues of eels in fresh water and sea water, with a view to assessing a possible role for the peptide in osmoregulation. Homogenates of gills and kidneys were incubated with bradykinin, and the nature of the metabolites determined by amino acid analysis and high performance liquid chromatography (HPLC) coelution profiles with standards. Homogenates from sea water and fresh water gills metabolized bradykinin at similar rates and the 2 major metabolites produced were similar. Sea water and fresh water eel renal homogenates also completely degraded bradykinin at similar rates. It appeared that the gills metabolized bradykinin in a slightly different fashion to the kidneys, but no inherent differences in overall rates were detectable. It was concluded that, although both the gills and kidneys may differentially process the kinin, a relationship to osmoregulation was not obvious.

Techniques to examine the biology of a kininogen homologue, cystatin C, were developed, and these have been used to investigate its actions. In addition, structure function studies have been used to localise binding sites for peptide ligands and non peptide antagonists.

It was concluded that the kallikrein kinin system and associated receptors appeared early in evolution. They share many of the characteristics of the mammalian system but important differences have been revealed which, when fully elucidated, are likely to provide important insights into physiological, pharmacological and molecular regulatory mechanisms of this peptide cascade.
NEANT

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITY OF SHEFFIELD
Address
Western Bank
S10 2TN Sheffield
United Kingdom

Participants (1)

COPENHAGEN UNIVERSITY HOSPITAL
Denmark
Address
Blegdamsvej 9
2100 Koepenhagen