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Elsevier, Toxicon: An Interdisciplinary Journal on the Toxins Derived from Animals, Plants and Microorganisms, (90), p. 36-44, 2014

DOI: 10.1016/j.toxicon.2014.07.011

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A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake)

This paper is available in a repository.
This paper is available in a repository.

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Abstract

Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date. The pharmacological effects of BPP-Cdc were compared to BBP9a from Bothrops Jararaca and captopril. BPP-Cdc (1μM) significantly increased BK-induced contractions (BK; 1μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10nM) by 62.4% and these effects were not significantly different from those of BPP9a (1μM) or captopril (200nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10ng) was decreased by 50μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50μg BPP9a (69.8%). However, the action duration of BPP-Cdc (60 min) was 2 times greater than that of BPP-9a (30 min). On the other hand, the hypotensive effect of BK (250ng) was significantly increased by 176.6% after BPP-Cdc (50μg) administration, value 2.5 times greater than that obtained with BPP9a administered at the same doses (71.4%). In addition, the duration of the action of BPP-Cdc (120 min) was also at least 4 times greater than that of BPP-9a (30 min). Taken together, these results suggest that BPP-Cdc presents more selective action on arterial blood system than BPP9a. Besides the inhibition of ACE, it may present other mechanisms of action yet to be elucidated.