Inhibition of acute nociceptive responses in rats after i.c.v. injection of Thr6-bradykinin, isolated from the venom of the social wasp, Polybia occidentalis.
OBJECTIVE
In this work, a neuroactive peptide from the venom of the neotropical wasp Polybia occidentalis was isolated and its anti-nociceptive effects were characterized in well-established pain induction models.


METHODS
Wasp venom was analysed by reverse-phase HPLC and fractions screened for anti-nociceptive activity. The structure of the most active fraction was identified by electron-spray mass spectrometry (ESI-MS/MS) and it was further assessed in two tests of anti-nociceptive activity in rats: the hot plate and tail flick tests.


RESULTS
The most active fraction contained a peptide whose structure was Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH, which corresponds to that of Thr(6)-BK, a bradykinin analogue. This peptide was given by i.c.v. injection to rats. In the tail flick test, Thr(6)-BK induced anti-nociceptive effects, approximately twice as potent as either morphine or bradykinin also given i.c.v. The anti-nociceptive activity of Thr(6)-BK peaked at 30 min after injection and persisted for 2 h, longer than bradykinin. The primary mode of action of Thr(6)-BK involved the activation of B(2) bradykinin receptors, as anti-nociceptive effects of Thr(6)-BK were antagonized by a selective B(2) receptor antagonist.


CONCLUSIONS
Our data indicate that Thr(6)-BK acts through B(2) bradykinin receptors in the mammalian CNS, evoking antinociceptive behaviour. This activity is remarkably different from that of bradykinin, despite the structural similarities between both peptides. In addition, due to the increased metabolic stability of Thr(6)-BK, relative to that of bradykinin, this peptide could provide a novel tool in the investigation of kinin pathways involved with pain.
Mortari
M R
MR
Neurobiology and Venoms Laboratory, Department of Biology, Faculty of Philosophy, Sciences and Literature of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Cunha
A O S
AO
Carolino
R O G
RO
Coutinho-Netto
J
J
Tomaz
J C
JC
Lopes
N P
NP
Coimbra
N C
NC
Dos Santos
W F
WF
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D016234:Kallikrein-Kinin System; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000187:drug effects / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014862:Wasp Venoms / Q000737:chemistry*
D000700:Analgesics; D043782:Receptor, Bradykinin B2; D014862:Wasp Venoms; C062689:bradykinin, Thr(6)-; D009020:Morphine; D001920:Bradykinin