Bradykinin potentiation

Scheme 13 Solid-Phase Synthesis of [gLys6,(f S)-mPhe7,Ala8]-Bradykinin Potentiating Peptide,.,161...

Certain pentapeptides potentiate the contractile response of isolated guinea-pig ileum to bradykinin [4, 5], The effects on bradykinin potentiation of varying the amino-acid sequence in the pentapeptide were investigated [6]. Each of the five amino acids was regarded as a substituent. By constructing a particular scale from the physicochemical properties of the amino acids, the variation in amino-acid sequence in the pentapeptides can be quantitatively described [6, 7]. 

Ferreira s interest in the physiology of bradykinin led him in the early 1960s to search for substances that would inhibit its in vivo inactivation. The venom of the Brazilian arrowhead viper Bothrops jararaca generates bradykinin in plasma, and Ferreira discovered that the venom itself contained substances capable of potentiating bradykinin-induced contractions of isolated guinea pig ileum. He and Rocha e Silva called the active fraction of this venom the bradykinin-potentiating factor (BPF) (75). 

Nine bradykinin-potentiating peptides (BPP5) were isolated from the Bothropos jararaca venom by Ferreira, Greene and co-workers (82,83). 

Kato, H. and Suzuki, T. 1971. Bradykinin-potentiating peptides from the venom of Agkistrodon halysblomhojfii. Isolation of five bradykinin potentiators and the amino acid sequences of two of them, potentiators B and C. Biochemistry 10, 972—980. 

Maruyama, S., Nakagomi, K., Tomizuka, N., and Suzuki, H. 1985. Angiotensin I-converting enzyme inhibitor derived from an enzymatic hydrolysate of casein. II. Isolation and bradykinin-potentiating activity on the uterus and the ileum of rats. Agric. Biol. Chem. Tokyo 49, 1405-1409. 

The teprotide BPP9a (bradykinin-potentiating peptide) 76 and analogous BPP peptides170), which have been isolated from snake venom, are taken up by ACE in competition with the substrate angiotensin I with far greater affinity. 

Hellberg, S., Sjostrom. M. and Wold. S. The Prediction of Bradykinin Potentiating Potency of Pentapeptides. An Example of a Peptide Quantitative Structure-Activity Relationship. Acta Chem. Scand. 1986, B40, 135-140. 

Norinder, U. (1991). Theoretical Amino Acid Descriptors. Application to Bradykinin Potentiating Peptides. Peptides, 12,1223-1227. 

ACE inhibitor drugs were developed by modelling interaction with the active site of the enzyme of a snake-venom-derived bradykinin-potentiating peptide, and from this the necessary structure of non-peptide inhibitors was inferred. The first such ACE inhibitor used medicinally was caplopril. Later examples in clinical use include cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril. Several ACE inhibitors are now administered clinically as prodrugs - which have good bioavailability, but are inactive in their own right. They are then converted to the active molecule in vivo, usually by esterases (e.g. enalapril to enalaprilat. and ramipril to ramiprilat). 

Thi ,DPhe BK [Thi ,DPhe ]-bradykinin. bradykinin-potentiating peptide teprotide. bradykinin potentiator B teprotide. BRADYKININ RECEPTOR AGONISTS act at sites recognizing members and derivatives of the bradykinin family of hormone peptides - kinins - of which bradykinin (BK) and kallidin (lysyl-bradykinin Lys-BK KD) are the main mammalian members. The bradykinin family is distinct from the tachykinin family of peptides, though both have profound hypotensive actions and contract many intestinal and other smooth muscles. Historically, it was noted that the former action was relatively slow-developing, hence the name bradykinin. Notable actions of bradykinin and kallidin are to dilate blood vessels and increase their permeability to plasma proteins, and to stimulate sensory nerve C-fibres. These actions are pro-inflammatory, and reflect the fact that the kinin-formation system is activated in inflammation, and enzymes (kallikreins) form the kinins from blood-borne or tissue precursors (kininogens) on injurious insult. 

Ferreira, S. H. A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca. Br. J. Pharmacol. Chemother. 1965,24, 163-169. 

The bradykinin potentiating effect of a series of peptides present in the venom of the South American poisonous snake Bothrops jararaca has already been mentioned in connection with the inhibition of the angiotensin converting enzyme (cf. p. 183) [33]. These proline rich peptides... 

Constit. of the venom of the snakes Bothrops insularis, Trimeresurus flavoviridis and T. okinavensis. Bradykinin potentiator. 

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