Premium
Selective release of ATP from sympathetic nerves of rat vas deferens by the toxin TsTX‐I from Brazilian scorpion Tityus serrulatus
Author(s) -
Conceição Isaltino M,
Jurkiewicz Aron,
Fonseca Daniela R,
Opperman Andrea R,
Freitas Thalma A,
Lebrun Ivo,
GarcezdoCarmo Lúcia
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706062
Subject(s) - vas deferens , purinergic receptor , veratridine , prazosin , chemistry , tetrodotoxin , suramin , pharmacology , medicine , endocrinology , adenosine , sodium channel , receptor , biology , antagonist , sodium , biochemistry , organic chemistry
1 The effects of the main component of the Tityus serrulatus scorpion venom, toxin TsTX‐I, were studied on the contractility and release of neurotransmitters in the rat vas deferens. Since TsTX‐I is known to act on sodium channels, we used veratridine, another sodium channel agent, for comparison. 2 Toxin TsTX‐I induced concentration‐dependent contractions with an EC 50 value of 47.8±0.1 n M and a maximum effect of 84.4±10.4% of that for BaCl 2 . 3 Contractions by TsTX‐I were abolished by denervation or tetrodotoxin (0.1 μ M ), showing that the toxin effects depend on the integrity of sympathetic nerve terminals. 4 To check for the presence of a noradrenergic component, experiments were conducted after removal of adrenergic stores in nerve terminals by reserpinization (10 mg kg −1 , 24 h prior to experiments) or blockade of α 1 adrenoceptors by prazosin (30 μ M ), showing that these procedures did not modify the response to TsTX‐I, and therefore that adrenoceptors were not involved in contractions. 5 To check for the presence of a purinergic component, experiments were carried out after blockade of P 2X receptors by suramin (0.1 m M ) or desensitization by α , β ‐methylene‐ATP (30 μ M ). These agents greatly abolished the contractile response to TsTX‐I (about 83% by desensitization and 96% by suramin), showing the involvement of purinergic receptors. 6 The release of noradrenaline and purinergic agents (ATP, ADP, AMP and adenosine) was detected by HPLC. Together, the total release of purines in the presence of TsTX‐I was about 42 times higher than in the control group. In contrast, TsTX‐I did not modify the overflow of noradrenaline, showing that the release was selective for purines. 7 The release of purinergic agents was reduced by the N‐type calcium channel blocker ω‐conotoxin GVIA (1 μ M ) and by the P/Q‐type blocker ω‐conotoxin MVIIC (1 μ M ), showing that the effects of TsTX‐I are calcium‐dependent. 8 The results show that TsTX‐I produced a selective release of purines from postganglionic sympathetic nerves in the rat vas deferens.British Journal of Pharmacology (2005) 144 , 519–527. doi: 10.1038/sj.bjp.0706062