A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake)
| Autor: | Bruno A. Cardi, Ellaine Dóris Fernandes Carvalho, Manassés C. Fonteles, Nilberto R.F. Nascimento, Paula Priscila Correia Costa, Krishnamurti M. Carvalho, Daniel C. Pimenta, Denise M. Lopes, Patricia Lustosa Martins, Cláudia F. Santos, Maria Denise Fernandes Carvalho, Norberto E.G. Junior |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Spectrometry Mass Electrospray Ionization Bradykinin Venom Ileum Blood Pressure Toxicology chemistry.chemical_compound Mice Internal medicine Renin–angiotensin system Crotalid Venoms medicine Viperidae Animals Amino Acid Sequence Rats Wistar Chromatography High Pressure Liquid biology Captopril Crotalus Angiotensin-converting enzyme biology.organism_classification Rats medicine.anatomical_structure Endocrinology chemistry Snake venom biology.protein Peptides medicine.drug Muscle Contraction |
| Zdroj: | Toxicon : official journal of the International Society on Toxinology. 90 |
| ISSN: | 1879-3150 |
| Popis: | 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 (1 μM) significantly increased BK-induced contractions (BK; 1 μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10 nM) by 62.4% and these effects were not significantly different from those of BPP9a (1 μM) or captopril (200 nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10 ng) was decreased by 50 μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50 μg 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 (250 ng) was significantly increased by 176.6% after BPP-Cdc (50 μg) 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. |
| Databáze: | OpenAIRE |
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