Bradykinin-related peptides in the venom of the solitary wasp Cyphononyx fulvognathus

• Published in: Biochemical pharmacology Vol. 79; no. 3; pp. 478 - 486
• Main Authors: Picolo, Gisele, Hisada, Miki, Moura, Analuê B., Machado, Maurício F.M., Sciani, Juliana M., Conceição, Isaltino M., Melo, Robson L., Oliveira, Vitor, Lima-Landman, Maria Teresa R., Cury, Yara, Konno, Katsuhiro, Hayashi, Mirian A.F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-02-2010; Elsevier
• Subjects: ACE inhibition; Amino Acid Sequence; Animals; Biological and medical sciences; Bradykinin; Bradykinin - analogs & derivatives; Bradykinin - isolation & purification; Bradykinin - physiology; Female; Gastrointestinal Motility - drug effects; Guinea Pigs; Hymenoptera; Hyperalgesia; Ileum - drug effects; Ileum - physiology; Ileum contraction; Male; Medical sciences; Molecular Sequence Data; Pain Measurement - methods; Peptides - isolation & purification; Peptides - physiology; Pharmacology. Drug treatments; Rabbits; Rats; Rats, Wistar; Solitary wasp venom; Wasp Venoms - isolation & purification; Wasp Venoms - pharmacology; Wasps; PSD; ACE; Solitary wasp venom; Ileum contraction; ACE inhibition; BK; CPY; TFA; HOE-140; Hyperalgesia; CPB; Bradykinin; FRET; Fmoc; Thr6-BK; HPLC; APM; CID; Nervous system diseases; Vasodilator agent; Peptides; WASP gene; Digestive system; Insecta; Peptide hormone; Animal origin; Small intestine; Neuropeptide; Ileum; Arthropoda; Venom; Vespidae; Inhibitor; Hymenoptera; Invertebrata; Vespa; Aculeata
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2009.08.020

Biochemical and pharmacological characterization of novel bradykinin-related peptides (BRP) named Cd-146, Thr6-BK, fulvonin and cyphokinin isolated from the venom of the solitary wasp Cyphononyx fulvognathus is described.
Bradykinin (BK) and its related peptides are widely distributed in venomous animals, including wasps. In fact, we have previously purified a novel BK-related peptide (BRP) named Cd-146 and the threonine6-bradykinin (Thr6-BK) from the venom of the solitary wasp Cyphononyx fulvognathus. Further survey of this same wasp venom extract allowed the structural characterization of two other novel BRPs, named here as fulvonin and cyphokinin. Biochemical characterization performed here showed that although the high primary structure similarity observed with BK, these wasp peptides are not good substrates for angiotensin I-converting enzyme (ACE) acting more likely as inhibitors of this enzyme. In pharmacological assays, only those more structurally similar to BK, namely cyphokinin and Thr6-BK, were able to promote the contraction of guinea-pig ileum smooth muscle preparations, which was completely blocked by the B2 receptors antagonist HOE-140 in the same way as observed for BK. Only fulvonin was shown to potentiate BK-elicited smooth muscle contraction. Moreover, the 2 new wasp BRPs, namely fulvonin and cyphokinin, as well as Cd-146 and Thr6-BK, showed hyperalgesic effect in the rat paw pressure test after intraplantar injection. This effect was shown here to be due to the action of these peptides on BK receptors, since the hyperalgesia induced by both Cd-146 and fulvonin was blocked by B1 receptor antagonist, while the effect of both cyphokinin and Thr6-BK was reversed by B2 antagonist. This data give support to a better understanding of the function and targets of the kinin-related peptides widely found in several insect venoms.