{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:43:50Z","timestamp":1773758630761,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4020,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The effect of <jats:italic>Tityus serrulatus<\/jats:italic> scorpion venom and its toxin components on the rabbit isolated corpus cavernosum was investigated by use of a bioassay cascade.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>Tityus serrulatus<\/jats:italic> venom (3\u2013100\u2003\u03bcg), acetylcholine (ACh; 0.3\u201330\u2003nmol) and glyceryl trinitrate (GTN; 0.5\u201310\u2003nmol) dose\u2010dependently relaxed rabbit isolated corpus cavernosum preparations precontracted with noradrenaline (3\u2003\u03bc<jats:sc>M<\/jats:sc>). The selective soluble guanylate cyclase inhibitor 1H\u2010[1,2,4] oxadiazolo [4,3,\u2010alquinoxalin\u20101\u2010one] (ODQ; 30\u2003\u03bc<jats:sc>M<\/jats:sc>) increased the basal tone of the rabbit isolated corpus cavernosum and abolished the relaxations induced by the agents mentioned above. Methylene blue (30\u2003\u03bc<jats:sc>M<\/jats:sc>) also inhibited the relaxations induced by <jats:italic>Tityus serrulatus<\/jats:italic> venom but, in contrast to ODQ, the inhibition was irreversible.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The non\u2010selective NO synthase (NOS) inhibitors N<jats:sup>\u03a9<\/jats:sup>\u2010nitro\u2010<jats:sc>L<\/jats:sc>\u2010arginine methyl ester (<jats:sc>L<\/jats:sc>\u2010NAME; 10\u2003\u03bc<jats:sc>M<\/jats:sc>) and N<jats:sup>G<\/jats:sup>\u2010iminoethyl\u2010<jats:sc>L<\/jats:sc>\u2010ornithine (<jats:sc>L<\/jats:sc>\u2010NIO; 30\u2003\u03bc<jats:sc>M<\/jats:sc>) also increased the tone of the rabbit isolated corpus cavernosum and markedly reduced both ACh\u2010 and <jats:italic>Tityus serrulatus<\/jats:italic> venom\u2010induced relaxations without affecting those evoked by GTN. The inhibitory effect was reversed by infusion of <jats:sc>L<\/jats:sc>\u2010arginine (300\u2003\u03bc<jats:sc>M<\/jats:sc>), but not <jats:sc>D<\/jats:sc>\u2010arginine (300\u2003\u03bc<jats:sc>M<\/jats:sc>). The neuronal NOS inhibitor 1\u2010(2\u2010trifluoromethylphenyl) imidazole (TRIM, 100\u2003\u03bc<jats:sc>M<\/jats:sc>) did not affect either the tone of the rabbit isolated corpus cavernosum or the relaxations induced by ACh, bradykinin (Bk), <jats:italic>Tityus serrulatus<\/jats:italic> venom and GTN. TRIM was approximately 1,000 times less potent than <jats:sc>L<\/jats:sc>\u2010NAME in inhibiting rabbit cerebellar NOS <jats:italic>in vitro<\/jats:italic>, as measured by the conversion of [<jats:sup>3<\/jats:sup>H]\u2010<jats:sc>L<\/jats:sc>\u2010arginine to [<jats:sup>3<\/jats:sup>H]\u2010<jats:sc>L<\/jats:sc>\u2010citrulline.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The protease inhibitor aprotinin (Trasylol; 10\u2003\u03bcg\u2003ml<jats:sup>\u22121<\/jats:sup>) and the bradykinin B<jats:sub>2<\/jats:sub> receptor antagonist Hoe 140 (<jats:sc>D<\/jats:sc>\u2010Arg\u2010[Hyp<jats:sup>3<\/jats:sup>,Thi<jats:sup>5<\/jats:sup>,<jats:sc>D<\/jats:sc>\u2010Tic<jats:sup>7<\/jats:sup>, Oic<jats:sup>8<\/jats:sup>]\u2010BK; 50\u2003n<jats:sc>M<\/jats:sc>) did not affect the rabbit isolated corpus cavernosum relaxations induced by <jats:italic>Tityus serrulatus<\/jats:italic> venom. The ATP\u2010dependent K<jats:sup>+<\/jats:sup> channel antagonist glibenclamide (10\u2003\u03bc<jats:sc>M<\/jats:sc>) and the Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup>\u2003\u2003channel antagonists apamin (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) and charybdotoxin (0.1\u2003\u03bc<jats:sc>M<\/jats:sc>) also failed to affect the venom\u2010induced relaxations. Similarly, the K<jats:sup>+<\/jats:sup> channel blocker tetraethylammonium (TEA; 10\u2003\u03bc<jats:sc>M<\/jats:sc>) had no effect on the venom\u2010induced relaxations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Capsaicin (3 and 10\u2003nmol) relaxed the rabbit isolated corpus cavernosum in a dose\u2010dependent and non\u2010tachyphylactic manner. Ruthenium red (30\u2003\u03bc<jats:sc>M<\/jats:sc>), an inhibitor of capsaicin\u2010induced responses, markedly reduced the relaxations caused by capsaicin, but failed to affect those induced by <jats:italic>Tityus serrulatus<\/jats:italic> venom. <jats:sc>L<\/jats:sc>\u2010NAME (10\u2003\u03bc<jats:sc>M<\/jats:sc>) had no effect on the capsaicin\u2010induced relaxations of the rabbit isolated corpus cavernosum.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The sodium channel blocker tetrodotoxin (TTX; 1\u2003\u03bc<jats:sc>M<\/jats:sc>) abolished the relaxations of the rabbit isolated corpus cavernosum induced by <jats:italic>Tityus serrulatus<\/jats:italic> venom without affecting those evoked by capsaicin, ACh and GTN. Tetrodotoxin (1\u2003\u03bc<jats:sc>M<\/jats:sc>) also promptly reversed the response to the venom when infused during the relaxation phase.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The bioassay cascade of the toxin components purified from <jats:italic>Tityus serrulatus<\/jats:italic> venom revealed that only fractions X, XI and XII caused dose\u2010dependent relaxations of the rabbit isolated corpus cavernosum and these were markedly reduced by either TTX (1\u2003\u03bc<jats:sc>M<\/jats:sc>) or <jats:sc>L<\/jats:sc>\u2010NAME (10\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results indicate that <jats:italic>Tityus serrulatus<\/jats:italic> scorpion venom (and the active fractions X, XI and XII) relaxes rabbit corpus cavernosum via the release of NO. This release is specifically triggered by the activation of capsaicin\u2010insensitive cavernosal non\u2010adrenergic non\u2010cholinergic (NANC) fibres, that may possibly be nitrergic neurones. <jats:italic>Tityus serrulatus<\/jats:italic> venom may therefore provide an important tool for understanding further the mechanism of NANC nitrergic nerve activation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>123<\/jats:bold>, 435\u2013442; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701623\">10.1038\/sj.bjp.0701623<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701623","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:19:31Z","timestamp":1106939971000},"page":"435-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Effect of <i>Tityus serrulatus<\/i> scorpion venom on the rabbit isolated corpus cavernosum and the involvement of NANC nitrergic nerve fibres"],"prefix":"10.1111","volume":"123","author":[{"given":"Cleber E.","family":"Teixeira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio C.","family":"Bento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo A B.","family":"Lopes\u2010Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone A.","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Von Eickestedt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo N.","family":"Muscar\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliane C.","family":"Arantes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose R.","family":"Giglio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edson","family":"Antunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilberto","family":"De Nucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(91)90169-C"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1995.75.1.191"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-0101(89)90102-5"},{"key":"e_1_2_6_5_1","first-page":"108","article-title":"The delay of the inactivation of Na+ channels by TsTx\u2010V, a new neurotoxin from Tityus serrulatus scorpion venom","volume":"31","author":"Arantes E.C.","year":"1993","journal-title":"Toxicon"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"12553","DOI":"10.1016\/S0021-9258(18)33546-4","article-title":"Tityus serrulatus venom contains two classes of toxins: Tityus\u03b3 toxin is a new tool with a very affinity for studying the Na+ channel","volume":"257","author":"Barhanin J.","year":"1982","journal-title":"J. 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