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1.
Rev. latinoam. psicopatol. fundam ; 23(4): 841-856, dez. 2020.
Artigo em Português | LILACS-Express | LILACS, Index Psicologia - Periódicos | ID: biblio-1156752

RESUMO

O artigo aborda as noções de trauma e testemunho elaborados por Sándor Ferenczi e os articula com o livro Svetlana Aleksiévitch acerca do desastre nuclear de Tchernóbil. Nosso objetivo foi demonstrar a validade das observações de Ferenczi em relação a um trauma coletivo, organizado em torno de três eixos: a dissimetria relacional, o processo de desmentido e o narcisismo ferido. Através da leitura do livro pode-se compreender como a escritora teve seu papel aproximado daquele designado por Ferenczi.


This article approaches the concepts of trauma and testimony as elaborated by Sándor Ferenczi and associates them to Svetlana Aleksiévitch's book about the nuclear disaster of Chernobyl. It aims to show the value of Ferenczi's observations on collective trauma by highlighting three topics: relational dissymmetry, process of denial and wounded narcissism. Aleksiévitch's book allowed us to understand in what ways the author's role resembles the one described by Ferenczi.


Cet article discute les notions de traumatisme et de témoignage tels que développés par Sándor Ferenczi et les compare avec le livre de Svetlana Aleksiévitch sur la catastrophe nucléaire de Tchernobyl. Notre but est de montrer la valeur des observations de Ferenczi sur le traumatisme collectif, organisé autour de trois points : la dissymétrie relationnelle, le processus de déni et le narcissisme blessé. La lecture du livre d'Aleksiévitch permet de comprendre la façon dont le rôle de l'auteur se rapproche de celui désigné par Ferenczi.


Este artículo analiza las nociones de trauma y testimonio, elaborados por Sándor Ferenczi, y se articula con el libro de Svetlana Aleksiévitch sobre el desastre nuclear de Chernóbil. Nuestro objetivo fue demostrar la vigencia de las observaciones de Ferenczi con relación a un trauma colectivo, organizándose alrededor de tres ejes: la asimetría relacional, el proceso de negación y el narcisismo herido. A través de la lectura del libro se puede entender que el papel de la escritora se acercaba al designado por Ferenczi.

2.
Memorandum ; 33: 68-89, out. 2017.
Artigo em Português | LILACS | ID: biblio-914033

RESUMO

Este artigo historiográfico tem como objetivo diferenciar a teoria da sedução de Freud e a teoria do trauma de Ferenczi, tendo em vista as frequentes confusões com que ambas são tratadas, e indicar a contribuição de Jean Laplanche em conciliar essas teorias em sua Teoria da Sedução Generalizada. Apesar de apresentarem a violência sexual como denominador comum, as teorias de Freud e de Ferenczi abarcam funcionamentos psíquicos diferentes e demandas clínicas peculiares, o que justifica as experiências clínicas que Ferenczi elaborou. Como resultado, consideramos que a teoria freudiana versa sobre um modo neurótico de funcionamento psíquico, enquanto a teoria de Ferenczi contempla as modalidades limites tão frequentes na clínica contemporânea. Ao final, expõem-se as ideias de Jean Laplanche, que articula ambas teorias em sua Teoria da Sedução Generalizada.(AU)


This historiographical article has the objective to distinguish Freud?s seduction theory of Ferenczi?s trauma theory, considering the constant confusions which both of them are taken, and indicate Jean Laplanche?s contribution by reconciling them in his Theory of Generalized Seduction.. Although they present the sexual violence as a commom denominator, Freud and Ferenczi?s theories embrace diferente psychic functionings as peculiar clinical demands, which justifies the clinical experimentation that Ferenczi worked through. As result, we consider that the freudian theory points to a neurotical way of psychic functioning, meanwhile Ferenczi?s theory contemplates borderline ways such ordinary in contemporary clinic. By the end, will expose some ideas of Jean Laplanche, who articulates both theories in his Theory of Generalized Seduction.(AU)


Assuntos
Psicologia
3.
Memorandum ; 33: 68-89, out. 2017.
Artigo em Português | Index Psicologia - Periódicos | ID: psi-71450

RESUMO

Este artigo historiográfico tem como objetivo diferenciar a teoria da sedução de Freud e a teoria do trauma de Ferenczi, tendo em vista as frequentes confusões com que ambas são tratadas, e indicar a contribuição de Jean Laplanche em conciliar essas teorias em sua Teoria da Sedução Generalizada. Apesar de apresentarem a violência sexual como denominador comum, as teorias de Freud e de Ferenczi abarcam funcionamentos psíquicos diferentes e demandas clínicas peculiares, o que justifica as experiências clínicas que Ferenczi elaborou. Como resultado, consideramos que a teoria freudiana versa sobre um modo neurótico de funcionamento psíquico, enquanto a teoria de Ferenczi contempla as modalidades limites tão frequentes na clínica contemporânea. Ao final, expõem-se as ideias de Jean Laplanche, que articula ambas teorias em sua Teoria da Sedução Generalizada.(AU)


This historiographical article has the objective to distinguish Freud‟s seduction theory of Ferenczi‟s trauma theory, considering the constant confusions which both of them are taken, and indicate Jean Laplanche‟s contribution by reconciling them in his Theory of Generalized Seduction.. Although they present the sexual violence as a commom denominator, Freud and Ferenczi‟s theories embrace diferente psychic functionings as peculiar clinical demands, which justifies the clinical experimentation that Ferenczi worked through. As result, we consider that the freudian theory points to a neuroticalway of psychic functioning, meanwhile Ferenczi‟s theory contemplates borderline ways such ordinary in contemporary clinic. By the end, will expose some ideas of Jean Laplanche, who articulates both theories in his Theory of Generalized Seduction.(AU)


Assuntos
Psicologia
4.
Psicol. estud ; 17(3): 435-443, jul.-set. 2012.
Artigo em Português | LILACS | ID: lil-671490

RESUMO

Este artigo visa argumentar como o sofrimento psíquico ocorre e é mantido por meio da dialética pulsional entre ligação e desligamento. Pela metodologia da "psicanálise extramuros", apresentamos um recorte literário da obra da escritora norte-americana Carson McCullers para ilustrar como uma tradução rígida pode se colocar como barreira ao processo retradutivo. Assim, o sofrimento psíquico, gerado pelos elementos desligados do inconsciente, não teria chance de adquirir uma nova tradução. Como resultado e com base na Teoria da Sedução Generalizada de Laplanche, articulamos que a dinâmica pulsional e os conteúdos desligados invadem o próprio campo da síntese tradutiva, mantendo o sofrimento psíquico constante.


This article aims to discuss how psychic suffering occurs and is maintained by the pulsional dialectics between connection and disconnection. Through the methodology of "psychoanalysis beyond walls", we present a literary extract of North American author Carson McCullers to illustrate how a rigid translation can be a barrier to the retranslative process. Therefore, the psychic suffering generated by the disconnected elements of the unconscious would not have the chance to acquire a new translation. As a result and based on Laplanche's Theory of Generalized Seduction, we articulate that pulsional dynamics and disconnected contents invade the own field of translative synthesis, keeping psychic suffering constant.


Este artículo pretende argumentar cómo el sufrimiento psíquico ocurre y se mantiene por medio de la dialéctica pulsional entre ligazón y desligazón. A través de la metodología del psicoanálisis "extramuros" presentamos un recorte literario de la obra de la escritora norteamericana Carson McCullers para ilustrar cómo una traducción rígida puede ponerse como barrera en contra el proceso retraductivo. Así, el sufrimiento psíquico generado por los elementos desligados del inconsciente no tendría oportunidad de adquirir una nueva traducción. Como resultado y basado en la Teoría de la Seducción Generalizada de Laplanche, articulamos que la dinámica pulsional y los contenidos desligados invaden el propio campo de la síntesis traductiva, manteniendo el sufrimiento psíquico constante.


Assuntos
Humanos , Masculino , Feminino , Psicanálise , Estresse Psicológico , Inconsciente Psicológico
5.
Psicol. estud ; 17(3): 435-443, jul.-set. 2012.
Artigo em Português | Index Psicologia - Periódicos | ID: psi-57635

RESUMO

Este artigo visa argumentar como o sofrimento psíquico ocorre e é mantido por meio da dialética pulsional entre ligação e desligamento. Pela metodologia da "psicanálise extramuros", apresentamos um recorte literário da obra da escritora norte-americana Carson McCullers para ilustrar como uma tradução rígida pode se colocar como barreira ao processo retradutivo. Assim, o sofrimento psíquico, gerado pelos elementos desligados do inconsciente, não teria chance de adquirir uma nova tradução. Como resultado e com base na Teoria da Sedução Generalizada de Laplanche, articulamos que a dinâmica pulsional e os conteúdos desligados invadem o próprio campo da síntese tradutiva, mantendo o sofrimento psíquico constante.(AU)


This article aims to discuss how psychic suffering occurs and is maintained by the pulsional dialectics between connection and disconnection. Through the methodology of "psychoanalysis beyond walls", we present a literary extract of North American author Carson McCullers to illustrate how a rigid translation can be a barrier to the retranslative process. Therefore, the psychic suffering generated by the disconnected elements of the unconscious would not have the chance to acquire a new translation. As a result and based on Laplanche's Theory of Generalized Seduction, we articulate that pulsional dynamics and disconnected contents invade the own field of translative synthesis, keeping psychic suffering constant.(AU)


Este artículo pretende argumentar cómo el sufrimiento psíquico ocurre y se mantiene por medio de la dialéctica pulsional entre ligazón y desligazón. A través de la metodología del psicoanálisis "extramuros" presentamos un recorte literario de la obra de la escritora norteamericana Carson McCullers para ilustrar cómo una traducción rígida puede ponerse como barrera en contra el proceso retraductivo. Así, el sufrimiento psíquico generado por los elementos desligados del inconsciente no tendría oportunidad de adquirir una nueva traducción. Como resultado y basado en la Teoría de la Seducción Generalizada de Laplanche, articulamos que la dinámica pulsional y los contenidos desligados invaden el propio campo de la síntesis traductiva, manteniendo el sufrimiento psíquico constante.(AU)


Assuntos
Humanos , Masculino , Feminino , Estresse Psicológico , Inconsciente Psicológico , Psicanálise
6.
Urology ; 74(1): 216-21, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19371941

RESUMO

OBJECTIVES: To compare the direct relaxant activity of sildenafil, vardenafil, and tadalafil in the human corpus cavernosum (HCC) and to investigate their modulatory effects on nitric oxide (NO)-mediated responses. Phosphodiesterase (PDE)-5 inhibitors cause cavernosal smooth muscle relaxation and penile erection. METHODS: HCC strips were mounted in 10-mL organ baths containing Krebs solution and connected to force-displacement transducers. The changes in isometric force were recorded using the Powerlab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 micromol/L). RESULTS: All PDE-5 inhibitors tested (0.001-10 micromol/L) relaxed phenylephrine-precontracted HCC with similar values of potency in a concentration-dependent manner. However, the maximal relaxations induced by tadalafil (83% +/- 4%) were significantly lower compared with sildenafil (107% +/- 5%) and vardenafil (111% +/- 3%). The NO synthesis inhibitor N-nitro-l-arginine methyl ester (100 micromol/L) caused significant rightward shifts in the concentration-response curves for sildenafil (4.0-fold), vardenafil (4.6-fold), and tadalafil (3.2-fold) in HCC tissue. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/L) also produced similar rightward shifts for these PDE-5 inhibitors. The cavernosal relaxations evoked by either acetylcholine or the NO donor glyceryl trinitrate were markedly potentiated by sildenafil, vardenafil, and tadalafil (0.1 micromol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz). CONCLUSIONS: Our findings have shown that sildenafil, vardenafil, and tadalafil relax HCC tissues in a concentration-dependent manner, but the maximal relaxation obtained with tadalafil was significantly lower than that obtained with sildenafil and vardenafil. Moreover, the PDE-5 inhibitors interacted with endogenous and exogenous NO, amplifying its HCC relaxation.


Assuntos
Carbolinas/farmacologia , Imidazóis/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Pênis/enzimologia , Pênis/fisiologia , Inibidores da Fosfodiesterase 5 , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/farmacologia , Sulfonas/farmacologia , Adolescente , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Pênis/efeitos dos fármacos , Purinas/farmacologia , Citrato de Sildenafila , Tadalafila , Triazinas/farmacologia , Dicloridrato de Vardenafila , Adulto Jovem
7.
J Med Chem ; 51(9): 2807-15, 2008 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-18393409

RESUMO

The 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7 H-pyrazolo[4,3-d]pyrimidin-7-one, sildenafil, is a cGMP-specific phosphodiesterase-5 (PDE5) inhibitor used for penile erectile dysfunction. In the search for more potent and selective PDE5 inhibitors, new sildenafil analogues (6a-v), characterized by the presence on the sulfonyl group in the 5' position of novel N-4-substituted piperazines or ethylenediamine moiety, were prepared by traditional and microwave-assisted synthesis and tested in rabbit isolated aorta and corpus cavernosum. Similarly to sildenafil, several analogues showed IC50 values in the nanomolar range. In the in vitro studies, all the tested compounds caused concentration-dependent relaxations in both rabbit isolated aorta and corpus cavernosum. All sildenafil analogues potentiated the nitric oxide-dependent vasodilation in endothelium-intact rabbit aorta. Compound 6f exhibited great pEC50 value in corpus cavernosum, and compounds 6r and 6u in isolated aorta were found as potent as sildenafil for inhibiting PDE5. Because several analogues were significantly more lipophilic than sildenafil, these compounds may offer a new lead for development of new sildenafil analogues.


Assuntos
Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5 , Piperazinas/síntese química , Pirimidinas/síntese química , Sulfonas/síntese química , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Plaquetas/efeitos dos fármacos , Plaquetas/enzimologia , Endotélio Vascular/fisiologia , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Masculino , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Pênis/efeitos dos fármacos , Pênis/fisiologia , Piperazinas/química , Piperazinas/farmacologia , Purinas/síntese química , Purinas/química , Purinas/farmacologia , Pirimidinas/química , Pirimidinas/farmacologia , Coelhos , Ratos , Citrato de Sildenafila , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade , Sulfonas/química , Sulfonas/farmacologia
8.
Eur J Pharmacol ; 530(1-2): 157-65, 2006 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-16371226

RESUMO

The compound BAY 41-2272 stimulates the soluble guanylyl cyclase in a nitric oxide (NO)-independent manner. We have investigated the potency and efficacy of BAY 41-2272 in the rat anococcygeus muscle, as well as the effects of BAY 41-2272 on NO-mediated anococcygeus relaxations. BAY 41-2272 (0.01-10 microM) potently relaxed precontracted anococcygeus muscle strips, with a pEC(50) value of 6.44 +/- 0.03 and maximum response of 100 +/- 2%. The soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxidiazolo[4,3-a] quinoxalin-1-one (ODQ, 1 microM) and the NO inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) caused significant rightward shifts in the concentration-response curves to BAY 41-2272. The phosphodiesterase type-5 inhibitor tadalafil (0.1 microM) markedly enhanced the relaxations evoked by BAY 41-2272. In addition, BAY 41-2272 increased the duration of nitrergic relaxations by approximately 55%. The relaxations induced by glyceryl trinitrate were also significantly potentiated by BAY 41-2272. In conclusion, BAY 41-2272 interacts with endogenous and exogenous NO causing a potent relaxation of rat anococcygeus muscle.


Assuntos
Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Óxido Nítrico/farmacologia , Pirazóis/farmacologia , Piridinas/farmacologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Carbacol/farmacologia , Carbolinas/farmacologia , Colforsina/farmacologia , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Estimulação Elétrica , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Guanilato Ciclase , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Nitroglicerina/farmacologia , Oxidiazóis/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Guanilil Ciclase Solúvel , Tadalafila , Tetrodotoxina/farmacologia
9.
Clin Exp Pharmacol Physiol ; 32(9): 728-34, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16173929

RESUMO

1. The compound BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine) has been described as a potent, nitric oxide (NO)-independent, stimulator of soluble guanylate cyclase. In the present study, the mechanisms underlying the relaxant effect of BAY 41-2272 in endothelium-intact and -denuded precontracted rabbit aortic rings were investigated. 2. Male New Zealand white rabbits were anaesthetized with pentobarbital sodium. Aortic rings were transferred to 10 mL organ baths containing oxygenated and warmed Krebs' solution. Tissues were connected to force-displacement transducers and changes in isometric force were recorded. Aortic rings were precontracted submaximally with phenylephrine (1 micromol/L). 3. The addition of BAY 41-2272 (0.01-10 micromol/L) to the organ bath produced concentration-dependent relaxations of the aortic rings with a higher potency in endothelium-intact (pEC50 6.59 +/- 0.05) compared with endothelium-denuded (pEC50 6.19 +/- 0.04; P < 0.05) preparations. No differences in maximal responses were observed in either preparation. The NO synthesis inhibitor NG-nitro-L-arginine methyl ester (100 micromol/L) produced a 2.1-fold rightward shift in endothelium-intact (P < 0.01) rings, but had no effect in endothelium-denuded rings. The soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 micromol/L) caused significant rightward shifts of the concentration-response curves to BAY 41-2272 of 4.9- and 2.6-fold in endothelium-intact and -denuded rings, respectively. The phosphodiesterase-5 inhibitor sildenafil (0.1 micromol/L) significantly potentiated the relaxant effects of BAY 41-2272 in both endothelium-intact and -denuded rings. 4. At 1 micromol/L, BAY 41-2272 significantly elevated the aortic cGMP content above basal levels in both endothelium-intact and -denuded rings. Furthermore, ODQ reduced BAY 41-2272-elicited increases in cGMP content by 17 and 90% in endothelium-intact and -denuded rings, respectively (P < 0.01). 5. In conclusion, BAY 41-2272 potently relaxes endothelium-intact and -denuded rabbit aortic rings. The basal release of endothelium-derived NO enhances BAY 41-2272-induced relaxations, suggesting a synergistic effect of BAY 41-2272 and NO on soluble guanylate cyclase. In addition, the endothelium-independent relaxation involves both GMP-dependent and -independent mechanisms.


Assuntos
Aorta/efeitos dos fármacos , Guanilato Ciclase/efeitos dos fármacos , Pirazóis/farmacologia , Piridinas/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/fisiologia , Oxidiazóis/farmacologia , Piperazinas/farmacologia , Purinas , Quinoxalinas/farmacologia , Coelhos , Transdução de Sinais , Citrato de Sildenafila , Sulfonas
10.
Eur J Pharmacol ; 519(1-2): 146-53, 2005 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-16084509

RESUMO

Beta-Adrenoceptor antagonists may present receptor-independent mechanisms, such as blockade of voltage-gated sodium channels. This study aimed to investigate the effects of non-selective (propranolol), and selective beta1- (atenolol, metoprolol and betaxolol) and beta2-adrenoceptor (ICI 118,551) antagonists in the nitric oxide (NO)-mediated rabbit corpus cavernosum relaxations induced by either electrical field stimulation (EFS) or activators of voltage-gated sodium channels. The sodium channel blockers tetrodotoxin and saxitoxin abolished the relaxations induced by EFS or sodium channel activators of binding site-2 (aconitine and veratridine), site-3 (Ts3 toxin), site-4 (Ts1 toxin) and site-5 (brevetoxin-3). The beta-adrenoceptor antagonists failed to affect the relaxations induced by EFS, aconitine and veratridine. Relaxations induced by Ts3 and Ts1 toxins, as well as brevetoxin-3, were markedly reduced by prior addition of propranolol, betaxolol and ICI 118,551. During the established relaxation induced by Ts3 toxin, propranolol failed to restore the basal tone. In conclusion, beta-adrenoceptor antagonists may cause an allosteric inhibition at the binding site-3, -4 and -5 of voltage-gated sodium channels, leading to blockade of neural NO release.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Óxido Nítrico/metabolismo , Pênis/efeitos dos fármacos , Agonistas de Canais de Sódio , Aconitina/farmacologia , Animais , Atenolol/farmacologia , Betaxolol/farmacologia , Sítios de Ligação , Estimulação Elétrica , Técnicas In Vitro , Proteínas de Insetos , Masculino , Metoprolol/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Neurotoxinas/farmacologia , Pênis/metabolismo , Pênis/fisiologia , Propanolaminas/farmacologia , Propranolol/farmacologia , Coelhos , Saxitoxina/farmacologia , Venenos de Escorpião/farmacologia , Tetrodotoxina/farmacologia , Veratridina/farmacologia
11.
J Pharmacol Exp Ther ; 309(2): 587-93, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-14752060

RESUMO

This study was performed to characterize the beta-adrenoceptor population in rabbit isolated corpus cavernosum (RbCC) by using nonselective and selective beta-adrenoceptor agonists and antagonists in functional assays. Metaproterenol, ritodrine, fenoterol, and 8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(rho-methoxyphenyl)-1-methylethyl]amino]ethyl]carbostyril (TA 2005) (3-100 nmol each) dose dependently relaxed the RbCC preparations. These relaxations were markedly reduced by N(omega)-nitro-L-arginine methyl ester (L-NAME; 10 microM) and 1H-[1,2,4]-oxadiazolo-[4,3,-a]quinoxalin-1-one (ODQ) (10 microM), whereas the adenylyl cyclase inhibitor SQ 22,536 [9-(2-tetrahydrofuryl) adenine] (10 microM) had no effect. In contrast, neither L-NAME nor ODQ affected the isoproterenol-induced RbCC relaxations, but SQ 22,536 abolished this response. Sildenafil (1 microM) significantly potentiated the relaxations induced by beta(2)-agonists without affecting the isoproterenol-evoked relaxations. Rolipram (10 microM) enhanced the relaxations elicited by isoproterenol but had no effect on those induced by the selective beta(2) agonists. Propranolol and (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride (ICI 118,551) determined a rightward shift in the concentration-response curves to isoproterenol in a noncompetitive manner with a reduction of maximum response at the highest antagonist concentration, with the slope values significantly different from unity. Propranolol and ICI 118,551 had no effect on the relaxations elicited by fenoterol, TA 2005, metaproterenol, and ritodrine. Atenolol and 1-[2-((3-carbamoyl-4-hydroxy)phenoxy) ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]-2-propanol methanesulfonate (CGP 20712A) (0.1-10 microM) failed to affect the relaxations induced by all tested beta-adrenoceptor agonists. Our study revealed the existence of two atypical beta-adrenoceptors in the rabbit erectile tissue. Isoproterenol relaxes the rabbit cavernosal tissue by activating atypical beta-adrenoceptors coupled to adenylyl cyclase pathway, whereas the selective beta(2)-adrenoceptor agonists relax the RbCC tissue through another atypical beta-adrenoceptor subtype coupled to nitric oxide release from the sinusoidal endothelium.


Assuntos
Relaxamento Muscular/fisiologia , Receptores Adrenérgicos beta/fisiologia , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , 3',5'-GMP Cíclico Fosfodiesterases , Adenilil Ciclases/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Interações Medicamentosas , Masculino , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico/fisiologia , Diester Fosfórico Hidrolases/metabolismo , Coelhos , Receptores Adrenérgicos beta/classificação , Bloqueadores dos Canais de Sódio/farmacologia
12.
Urology ; 63(1): 184-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14751389

RESUMO

OBJECTIVES: 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.


Assuntos
Neurotoxinas/farmacologia , Óxido Nítrico/metabolismo , Pênis/efeitos dos fármacos , Venenos de Escorpião/farmacologia , Adolescente , Adulto , Criança , GMP Cíclico/fisiologia , Avaliação Pré-Clínica de Medicamentos , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Humanos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/farmacologia , Óxido Nítrico/fisiologia , Oxidiazóis/farmacologia , Pênis/metabolismo , Fenilefrina/farmacologia , Piperazinas/farmacologia , Priapismo/tratamento farmacológico , Purinas , Quinoxalinas/farmacologia , Sistemas do Segundo Mensageiro/fisiologia , Citrato de Sildenafila , Bloqueadores dos Canais de Sódio/farmacologia , Sulfonas , Tetrodotoxina/farmacologia
13.
Eur J Pharmacol ; 477(2): 163-9, 2003 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-14519420

RESUMO

5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) is a potent soluble guanylyl cyclase stimulator in a nitric oxide (NO)-independent manner. The relaxant effect of BAY 41-2272 was investigated in rabbit and human corpus cavernosum in vitro. BAY 41-2272 (0.01-10 microM) relaxed both rabbit (pEC(50)=6.82+/-0.06) and human (pEC(50)=6.12+/-0.10) precontracted cavernosal strips. The guanylyl cyclase inhibitor (ODQ, 10 microM) caused significant rightward shifts in the concentration-response curves for BAY 41-2272 in rabbit (4.7-fold) and human (2.3-fold) tissues. The NO synthesis inhibitor (N-nitro-L-arginine methyl ester (L-NAME), 100 microM) also produced similar rightward shifts, revealing that BAY 41-2272 acts synergistically with endogenous NO to elicit its relaxant effect. The results also indicate that ODQ is selective for the NO-stimulated enzyme, since relaxations evoked by BAY 41-2272 were only partly attenuated by ODQ. The present study shows that both BAY 41-2272 and sildenafil evoke relaxations independent of inhibition of haem in soluble guanylate cyclase. Moreover, there is no synergistic effect of the two compounds in corpus cavernosum.


Assuntos
Ativadores de Enzimas/farmacologia , Guanilato Ciclase/metabolismo , Pênis/efeitos dos fármacos , Pirazóis/farmacologia , Piridinas/farmacologia , Adolescente , Adulto , Idoso , Animais , AMP Cíclico/metabolismo , Sinergismo Farmacológico , Guanilato Ciclase/antagonistas & inibidores , Humanos , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Relaxamento Muscular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Oxidiazóis/farmacologia , Pênis/fisiologia , Coelhos
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