Selective release of ATP from sympathetic nerves of rat vas deferens by the toxin TsTX-I from Brazilian scorpion Tityus serrulatus.
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 nM 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 microM), 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 alpha(1) adrenoceptors by prazosin (30 microM), 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 mM) or desensitization by alpha,beta-methylene-ATP (30 microM). 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 omega-conotoxin GVIA (1 microM) and by the P/Q-type blocker omega-conotoxin MVIIC (1 microM), 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.
Conceição
Isaltino M
IM
Laboratory of Pharmacology, Unit of Mode of Toxin Action (MATx), Butantan Institute, São Paulo, Brazil.
Jurkiewicz
Aron
A
Fonseca
Daniela R
DR
Opperman
Andrea R
AR
Freitas
Thalma A
TA
Lebrun
Ivo
I
Garcez-do-Carmo
Lúcia
L
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism; D012604:Scorpion Venoms / Q000302:isolation & purification / Q000494:pharmacology*; D012605:Scorpions / Q000378:metabolism*; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018377:Neurotransmitter Agents; D011941:Receptors, Adrenergic; D011983:Receptors, Purinergic; D012604:Scorpion Venoms; C482042:TsTX-I, mouse; D014701:Veratridine; D000255:Adenosine Triphosphate