Erectile Function Is Improved in Aged Rats by PnTx2-6, a Toxin from Phoneutria nigriventer Spider Venom

Kenia P. Nunes, Haroldo Alfredo Flores Toque, Marcia H. Borges, Michael Richardson, R Clinton Webb, Maria Elena de Lima

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Introduction. Age-associated erectile dysfunction (ED) involves a decrease in nitric oxide (NO) availability and impaired relaxation. PnTx2-6, a toxin from the Phoneutria nigriventer spider, has been demonstrated to improve erectile function via NO/cyclic guanosine monophosphate (cGMP) pathway. This spider's venom is characterized by several symptoms, including erection. PnTx2-6 has been implicated in this phenomenon. Animal venoms have been postulated as potential drugs to treat ED. Aim. PnTx2-6 toxin improves erectile function in aged rats via NO/cGMP. We investigated the effect of PnTx2-6 in the erectile function of aged rats. Main Outcome Measures. ED was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio during electrical field stimulation (EFS) of the pelvic ganglion of aged and adult rats (70 vs. 14 weeks). In functional studies, EFS-induced relaxation of corpus cavernosum (CC) strips were performed with or without PnTx2-6 (10-8M). Results. The decrease in erectile function associated with age was partially restored 15-20 minutes after injection of PnTx2-6 and further improved by sildenafil. PnTx2-6 enhanced EFS-induced relaxation, as well as cGMP levels in CC, from young and aged rats. Relaxation due to PnTx2-6 was further increased after 30 minutes incubation with Y-27632, a Rho-kinase inhibitor (10-6 M), in aging CC. Nitric oxide synthase (NOS) activity in aged and young cavernosal tissue was increased by incubation with PnTx2-6 (10 minutes). However, this toxin did not modify NOS expression. Conclusion. PnTx2-6 improves penile relaxation in aged rats, via increased NOS activity and NO release, resulting in enhanced cGMP levels.

Original languageEnglish (US)
Pages (from-to)2574-2581
Number of pages8
JournalJournal of Sexual Medicine
Volume9
Issue number10
DOIs
StatePublished - Jan 1 2012

Fingerprint

Spider Venoms
Cyclic GMP
Nitric Oxide
Erectile Dysfunction
Nitric Oxide Synthase
Electric Stimulation
rho-Associated Kinases
Spiders
Venoms
Ganglia
Arterial Pressure
Outcome Assessment (Health Care)
4-(3'-di(2-bromoethyl)aminopropionyl)biphenyl
Pressure
Injections
Pharmaceutical Preparations

Keywords

  • Aging
  • Cavernosal Smooth Muscle
  • Nitric Oxide
  • PnTx2-6 Toxin

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

Erectile Function Is Improved in Aged Rats by PnTx2-6, a Toxin from Phoneutria nigriventer Spider Venom. / Nunes, Kenia P.; Flores Toque, Haroldo Alfredo; Borges, Marcia H.; Richardson, Michael; Webb, R Clinton; de Lima, Maria Elena.

In: Journal of Sexual Medicine, Vol. 9, No. 10, 01.01.2012, p. 2574-2581.

Research output: Contribution to journalArticle

Nunes, Kenia P. ; Flores Toque, Haroldo Alfredo ; Borges, Marcia H. ; Richardson, Michael ; Webb, R Clinton ; de Lima, Maria Elena. / Erectile Function Is Improved in Aged Rats by PnTx2-6, a Toxin from Phoneutria nigriventer Spider Venom. In: Journal of Sexual Medicine. 2012 ; Vol. 9, No. 10. pp. 2574-2581.
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abstract = "Introduction. Age-associated erectile dysfunction (ED) involves a decrease in nitric oxide (NO) availability and impaired relaxation. PnTx2-6, a toxin from the Phoneutria nigriventer spider, has been demonstrated to improve erectile function via NO/cyclic guanosine monophosphate (cGMP) pathway. This spider's venom is characterized by several symptoms, including erection. PnTx2-6 has been implicated in this phenomenon. Animal venoms have been postulated as potential drugs to treat ED. Aim. PnTx2-6 toxin improves erectile function in aged rats via NO/cGMP. We investigated the effect of PnTx2-6 in the erectile function of aged rats. Main Outcome Measures. ED was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio during electrical field stimulation (EFS) of the pelvic ganglion of aged and adult rats (70 vs. 14 weeks). In functional studies, EFS-induced relaxation of corpus cavernosum (CC) strips were performed with or without PnTx2-6 (10-8M). Results. The decrease in erectile function associated with age was partially restored 15-20 minutes after injection of PnTx2-6 and further improved by sildenafil. PnTx2-6 enhanced EFS-induced relaxation, as well as cGMP levels in CC, from young and aged rats. Relaxation due to PnTx2-6 was further increased after 30 minutes incubation with Y-27632, a Rho-kinase inhibitor (10-6 M), in aging CC. Nitric oxide synthase (NOS) activity in aged and young cavernosal tissue was increased by incubation with PnTx2-6 (10 minutes). However, this toxin did not modify NOS expression. Conclusion. PnTx2-6 improves penile relaxation in aged rats, via increased NOS activity and NO release, resulting in enhanced cGMP levels.",
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T1 - Erectile Function Is Improved in Aged Rats by PnTx2-6, a Toxin from Phoneutria nigriventer Spider Venom

AU - Nunes, Kenia P.

AU - Flores Toque, Haroldo Alfredo

AU - Borges, Marcia H.

AU - Richardson, Michael

AU - Webb, R Clinton

AU - de Lima, Maria Elena

PY - 2012/1/1

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N2 - Introduction. Age-associated erectile dysfunction (ED) involves a decrease in nitric oxide (NO) availability and impaired relaxation. PnTx2-6, a toxin from the Phoneutria nigriventer spider, has been demonstrated to improve erectile function via NO/cyclic guanosine monophosphate (cGMP) pathway. This spider's venom is characterized by several symptoms, including erection. PnTx2-6 has been implicated in this phenomenon. Animal venoms have been postulated as potential drugs to treat ED. Aim. PnTx2-6 toxin improves erectile function in aged rats via NO/cGMP. We investigated the effect of PnTx2-6 in the erectile function of aged rats. Main Outcome Measures. ED was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio during electrical field stimulation (EFS) of the pelvic ganglion of aged and adult rats (70 vs. 14 weeks). In functional studies, EFS-induced relaxation of corpus cavernosum (CC) strips were performed with or without PnTx2-6 (10-8M). Results. The decrease in erectile function associated with age was partially restored 15-20 minutes after injection of PnTx2-6 and further improved by sildenafil. PnTx2-6 enhanced EFS-induced relaxation, as well as cGMP levels in CC, from young and aged rats. Relaxation due to PnTx2-6 was further increased after 30 minutes incubation with Y-27632, a Rho-kinase inhibitor (10-6 M), in aging CC. Nitric oxide synthase (NOS) activity in aged and young cavernosal tissue was increased by incubation with PnTx2-6 (10 minutes). However, this toxin did not modify NOS expression. Conclusion. PnTx2-6 improves penile relaxation in aged rats, via increased NOS activity and NO release, resulting in enhanced cGMP levels.

AB - Introduction. Age-associated erectile dysfunction (ED) involves a decrease in nitric oxide (NO) availability and impaired relaxation. PnTx2-6, a toxin from the Phoneutria nigriventer spider, has been demonstrated to improve erectile function via NO/cyclic guanosine monophosphate (cGMP) pathway. This spider's venom is characterized by several symptoms, including erection. PnTx2-6 has been implicated in this phenomenon. Animal venoms have been postulated as potential drugs to treat ED. Aim. PnTx2-6 toxin improves erectile function in aged rats via NO/cGMP. We investigated the effect of PnTx2-6 in the erectile function of aged rats. Main Outcome Measures. ED was evaluated through changes in intracavernosal pressure/mean arterial pressure ratio during electrical field stimulation (EFS) of the pelvic ganglion of aged and adult rats (70 vs. 14 weeks). In functional studies, EFS-induced relaxation of corpus cavernosum (CC) strips were performed with or without PnTx2-6 (10-8M). Results. The decrease in erectile function associated with age was partially restored 15-20 minutes after injection of PnTx2-6 and further improved by sildenafil. PnTx2-6 enhanced EFS-induced relaxation, as well as cGMP levels in CC, from young and aged rats. Relaxation due to PnTx2-6 was further increased after 30 minutes incubation with Y-27632, a Rho-kinase inhibitor (10-6 M), in aging CC. Nitric oxide synthase (NOS) activity in aged and young cavernosal tissue was increased by incubation with PnTx2-6 (10 minutes). However, this toxin did not modify NOS expression. Conclusion. PnTx2-6 improves penile relaxation in aged rats, via increased NOS activity and NO release, resulting in enhanced cGMP levels.

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KW - PnTx2-6 Toxin

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