Nitric oxide release from human corpus cavernosum induced by a purified scorpion toxin.
OBJECTIVE
To investigate the effects of a purified scorpion toxin (Ts3) on human corpus cavernosum (HCC) in vitro. Scorpion venoms cause a massive release of neurotransmitters that contribute to the clinical symptoms resulting from envenomation.


METHODS
HCC strips were mounted in organ baths containing Krebs solution. After equilibration, the tissues were precontracted with phenylephrine (10 micromol/L). The relaxations caused by Ts3 (30 nmol/L) were compared with those induced by electrical field stimulation (1 to 20 Hz) and nitric oxide (NO, 1 to 100 micromol/L).


RESULTS
The addition of Ts3 evoked long-lasting relaxations of precontracted HCC strips, and exogenously applied NO and electrical field stimulation caused short-lived responses. The NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 micromol/L) reduced by 87% +/- 2% the Ts3-induced relaxations; this inhibition was reversed by pretreating the tissues with L-arginine (1 mmol/L). The relaxant responses mediated by Ts3 were blocked to a similar degree by the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-alquinoxalin-1-one] (10 micromol/L). In contrast, the addition of the phosphodiesterase type 5 inhibitor sildenafil (0.1 micromol/L) significantly enhanced Ts3-evoked relaxations by 78% +/- 4%. The sodium channel blocker tetrodotoxin (1 micromol/L) completely blocked the relaxant responses elicited by both Ts3 and electrical field stimulation, without significantly affecting those elicited by NO.


CONCLUSIONS
The results indicate that Ts3 relaxes the HCC through the release of NO from nitrergic nerves. The elucidation of this mechanism is useful for the development of new therapeutic strategies to treat priapism after scorpion envenomation or to modulate sodium channel activity in the case of penile dysfunction.
Teixeira
Cleber E
CE
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas, São Paulo, Brazil.
de Oliveira
Juliano F
JF
Baracat
Juliana S
JS
Priviero
Fernanda B M
FB
Okuyama
Cristina E
CE
Rodrigues Netto
Nelson
N
Fregonesi
Adriano
A
Antunes
Edson
E
De Nucci
Gilberto
G
D000293:Adolescent; D000328:Adult; D002648:Child; D006152:Cyclic GMP / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D010069:Oxadiazoles / Q000494:pharmacology; D010413:Penis / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011317:Priapism / Q000188:drug therapy; D011687:Purines; D011810:Quinoxalines / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology*; D015290:Second Messenger Systems / Q000502:physiology; D000068677:Sildenafil Citrate; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013450:Sulfones; D013779:Tetrodotoxin / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D009498:Neurotoxins; D010069:Oxadiazoles; D010879:Piperazines; D011687:Purines; D011810:Quinoxalines; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D013450:Sulfones; C485970:Ts3 toxin, Tityus serrulatus; D010656:Phenylephrine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester