Bradykinin-Potentiating Peptides (BPPs)、緩激肽增強(qiáng)肽

Definition

Bradykinin potentiating peptides (BPPs) isolated from the venom of the snake, Bothrops jararaca increase both the duration and magnitude of bradykinin’s (Nonapeptide found in the blood plasma of animals after injection of venom) effects on vasodilation and the consequent fall in blood pressure1.

Discovery

BPPs were discovered in partially purified preparations of Bothrops jararaca venom by their ability to increase bradykinin activity in vitro in guinea pig ileum and in vivo in rats1. 

Classification

BPPs are naturally occurring inhibitors of angiotensin-converting enzyme (ACE) 2.  They present a classic motif and can be recognized by their pyroglutamyl rich sequences2. 

Structural Characteristics

BPPs are short 5-13 amino acid peptides with a proline rich sequence3. They have a cyclised form of glutamic acid as their N-terminus. For example, the structure of an active BPP pentapeptide is pyrrolidone-carboxyl-Lys-Trp-Ala-Pro3.

Mode of action

BPPs potentiate bradykinin activity primarily by blocking the function of kininase enzymes which are inhibitors of bradykinin4.  They are also known to increase bradykinin’s affinity to its receptors by promoting their sensitization4. 

Functions

The chemical and pharmacological properties of BPPs were used for the development of captopril, the first active site directed inhibitor of ACE, currently used to treat human hypertension5.  BPPs increase bradykinin activity in non-vascular smooth muscle contraction, vasodilation and lowering of blood pressure6. 

References

1. Ferreira, SH (1965). Bradykinin-potentiating factor (BPF) present in venom of Bothropsjararaca. Br. J. Pharmac. Chemother., 24, 163-169.

2. Katia C, Katsuhiro K, Robson Lopes DM, Marta MA, Carlos J, Juliana MS, Isaltino MC, Benedito CP, Antônio CMDC and Daniel CP (2006). Isolation and characterization of a novel bradykinin potentiating peptide (BPP) from the skin secretion of Phyllomedusa hypochondrialis. Peptides, 28, 3, 515-523.

3. Lewis JG, Sergio HF and John MS (1971). Bradykinin Potentiating Factor. Chest, 59;9S-10S.

4. Camargo A and Ferreira SH (1971). Action of bradykinin potentiating factor (BPF) and dimercaprol (BAL) on the responses to bradykinin of isolated preparations of rat intestines. Br J Pharmacol., 42(2): 305–307.

5. Fernandez JH, Neshich G and Camargo ACM (2004). Using bradykinin-potentiating peptide structures to develop new antihypertensive drugs. Genet. Mol. Res., 3 (4): 554-563.

6. Mueller S, Gothe R, Siems WD, Vietinghoff G, Paegelow I, Reissmann S (2005). Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP9 alpha. Peptides, 26(7):1235-47.