Studies on the inactivation of vasoactive polypeptides by pyridoxal-5'-phosphate.
The pharmacologically active peptides bradykinin (BK) lysylbradykinin or kallidin (LBK) and methionyl-lysylbradykinin (MLBK) were shown to react with pyridoxal-5'-phosphate (PLP) forming Schiff bases; upon reduction with sodium borohydride they were transformed into stable phosphopyridoxyl-kinins (PP-BK, PP-LBK and PP-MLBK). Amino acid analysis showed that the N-terminal alpha-aminogroup of the three kinins were efficiently blocked by phosphopyridoxyl groups: 98.8% for BK; 95.2% for LBK and 98.9% for MLBK. Guanidinium groups did not react with PLP. Estimated by guinea-pig ileum and the vascular permeability of rat skin assays respectively- the PP-kinins had the following average activities compared to the respective kinins: PP-BK, 0.20 and 0.16; PP-LBK, 0.05 and 0.17; PP-MLBK, 0.10 and 0.12. Isoleucyl5-angiotensin II and valyl5-angiotensin I were shown to be 50% inactivated (guinea-pig ileum assay) by reaction with PLP and reduction with borohydride.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001894:Borohydrides; D002199:Capillary Permeability / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006146:Guanidines / Q000032:analysis; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007705:Kinins / Q000032:analysis; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010455:Peptides / Q000037:antagonists & inhibitors*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects
D000596:Amino Acids; D001894:Borohydrides; D006146:Guanidines; D007705:Kinins; D010455:Peptides; D011732:Pyridoxal Phosphate