Pharmacological properties of a new kinin-potentiating peptide generated from human serum proteins.
A kinin-potentiating peptide (KPP) generated from human plasma proteins on trypsin incubation was partially purified by ultrafiltration and ion-exchange chromatography and was characterized through some of its pharmacological properties. KPP itself was devoid of any action but it potentiated the guinea-pig ileum contractions elicited by several kinins, including an analog resistant to angiotensin-converting enzyme (ACE). In contrast, contractions induced by angiotensin II, histamine, acetylcholine, barium chloride and substance P were not potentiated. Not only did KPP have high specificity towards kinins, but its action started immediately and induced kinin potentiation in a dose-dependent and reversible manner. Furthermore KPP potentiated the bradykinin contracting effects on the rat uterus, a preparation with very poor ACE activity, and on guinea-pig ileum previously incubated with 1.10-phenanthroline, a metal chelator able to inhibit ACE and kininase I activities and with phosphoramidon, a specific inhibitor of neutral endopeptidase (NEP). The results suggest that the potentiating effect of KPP is due to a mechanism different from the inhibition of kinin metabolism by ACE, NEP and kininase I.
Assreuy
J
J
Department of Biochemistry, Universidade Federal do Rio de Janeiro, Brazil.
Almeida
A A
AA
Guimarães
J A
JA
D001798:Blood Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D007705:Kinins / Q000378:metabolism; D009842:Oligopeptides / Q000302:isolation & purification / Q000494:pharmacology*; D013379:Substrate Specificity
D001798:Blood Proteins; D004798:Enzymes; D007705:Kinins; D009842:Oligopeptides; C006791:bradykinin potentiating factors