ISOLATION AND CHARACTERIZATION OF A NOVEL BRADYKININ POTENTIATING PEPTIDE FROM THE SKIN SECRETION OF Phyllomedusa hypochondrialis

CONCEIÇÃO K. (1), KONNO K. (1), MELO R.L. (1), ANTONIAZZI M.M. (2), JARED C. (2), SCIANI J.M. (3), CONCEIÇÃO I.M (3), PREZOTO B.C. (3), CAMARGO A.C.M.(1), PIMENTA D.C. (1)

(1) LETA - CAT/CEPID; (2) Depto. De Biologia Celular, (3) Lab de Farmacologia., Instituto Butantan, São Paulo, SP.

Bradykinin is often associated to inflammatory processes. Classical studies showed that there existed a factor in the venom of B. jararaca which potentiated bradykinin. This factor (BPPs) could inhibit the angiotensin-converting enzyme. We describe the isolation and biochemical characterization of a novel BPP, from the skin of P. hypochondrialis. Glandular secretions of P. hypochondrialis specimens were purified by rp-HPLC after solid phase extraction. MALDI-MS fingerprinting was performed and peptides were sequenced on a ESI-Q-TOF-MS/MS. BK potentiation was assessed by guinea-pig ileum contraction and by MAP measurements on anesthetized rats. We were able to purify and characterize a novel BPP from the skin secretion of P. hypochondrialis that was able to inhibit ACE, lower the blood pressure and potentiate smooth muscle contraction. The skin secretions of the members of the Phyllomedusinae frog family are widely known to be one the richest sources of bioactive peptides. This novel peptide has a typical BPP motif. Moreover, in vivo and in vitro assays were able to clearly demonstrate that this peptide meets all the functional requirements for a bioactive BPP. And mostly important, physiologically, at the level of the frog skin and its mechanisms of defense, the presence of BPPs can make all the well documented BKs and BRPs extremely powerfull weapons.

KEY WORDS: Amphibian; Bradykinin potentiating peptide; Phyllomedusa hypochondrialis

FINANCIAL SUPPORT: FAPESP, CAPES and CNPq.

CORRESPONDENCE TO: dcpimenta@butantan.gov.br