Im. Matos et al., Pharmacological evidence that neuropeptides mediate part of the actions ofscorpion venom on the guinea pig ileum, EUR J PHARM, 368(2-3), 1999, pp. 231-236
Severe human scorpion envenoming is characterised by instability of several
physiological systems and death. These manifestations are explained by the
ability of the venom toxins to activate sodium channels in nerve terminals
with the subsequent release of neurotransmitters, specially acetylcholine
and noradrenaline. However, there is evidence to suggest that other neurotr
ansmitters are also released. We now have sought evidence for a role of the
substance P receptor, the tachykinin NK1 receptor, in mediating part of th
e contractile actions of Tityus serrulatus venom on the isolated guinea pig
ileum. Scorpion venom induced a significant elevation of baseline tension
with frequent and periodic superimposed contractions on the elevated baseli
ne. Pretreatment with atropine partially blocked the elevation in baseline
and in the number of superimposed contractions. These responses were also p
artially inhibited by the tachykinin NK1 receptor antagonist, CP96,345 (the
dihydrochloride salt of (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl
)methyl)- 1-azabicycol[2.2.2]octan-3-amine). but not by its inactive enanti
omer, CP96,344 (the 2R-3R enantiomer of CP96,345). Pretreatment with the co
mbination of atropine and CP96,345 completely inhibited the effects of the
venom. Moreover, pretreatment with the combined drugs abolished the effects
of toxin gamma, a toxin purified from the venom. Finally, another tachykin
in NK1 receptor antagonist, RP67,580 ((3aR, 7ar)-7,7-diphenyl-2-[1-imino-2-
(2-methoxy-phenyl)ethyl]perhydroisoindol-4-one), significantly inhibited th
e venom-induced contractions. These results demonstrate an important role f
or NK1 receptors in mediating part of the contractile effects of the venom
on guinea pig ileum. The release of neuropeptides may play an important rol
e in the systemic manifestations of severe envenoming. (C) 1999 Elsevier Sc
ience B.V. All rights reserved.