Navegando por Palavras-chave "Rat vas deferens"
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- ItemSomente MetadadadosAllosteric interaction of the anticholinergic drug [N-(4-phenyl)-phenacyl-1-hyoscyamine] (Phenthonium) with nicotinic receptors of post-ganglionic sympathetic neurons of the rat vas deferens(Elsevier B.V., 2009-08-15) Munhoz, Egberto; De Lima, Thereza C. M.; Souccar, Caden; Lapa, Antonio J.; Lima-Landman, Maria Teresa R. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Santa Catarina (UFSC)Phenthonium (Phen), a quaternary analog of hyoscyamine, is a blocker of muscarinic activity and an allosteric blocker of alpha(1)2 beta gamma epsilon nicotinic receptors. Specifically, Phenthonium increases the spontaneous release of acetylcholine at the motor endplate without depolarizing the muscle or inhibiting cholinesterase activity. This paper compares Phenthonium's effects on sympathetic transmission and on ganglionic nicotinic receptor activation. Neurotransmitter release and twitch of the rat vas deferens were induced either by electrical stimulation or by 1,1-dimethyl-4-phenylpiperazine (DMPP) activation of nicotinic receptors. Contractions independent of transmitter release were induced by noradrenaline and adenosine 5'-triphosphate (ATP). Phenthonium inhibited transmitter release and depressed twitch without changing the responsiveness to noradrenaline or ATP. Twitch depression did not occur after K(+)-channel blockade with 4-aminopyridine (4-AP) or charybdotoxin. DMPP had a similar effect, but high concentrations induced contraction of non-stimulated organs. Incubation of Phenthonium inhibited further DMPP twitch depression and non-competitively depressed the contractile responses elicited by DMPP. Furthermore, mecamylamine, but neither methyllycaconitine nor atropine, blocked the contraction elicited by DMPP. Phenthonium and DMPP are K(+)-channel openers that primarily inhibit sympathetic transmission. Contraction induced by DMPP was probably mediated by neuronal nicotinic receptor other than the alpha 7 subtype. the blockade of DMPP contractile response was unrelated to Phenthonium's antimuscarinic or K(+)-channel opening activities. Since Phenthonium's quaternary chemical structure limits its membrane diffusion, the non-competitive inhibition of DMPP excitatory responses should be linked to allosteric interaction with neuronal nicotinic receptors that putatively qualify Phenthonium as a novel modulator of cholinergic synapses. (C) 2009 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosEffects of novel tacripyrines ITH12117 and ITH12118 on rat vas deferens contractions, calcium transients and cholinesterase activity(Elsevier B.V., 2011-06-25) Pereira, Janaina Drawanz [UNIFESP]; Caricati-Neto, Afonso [UNIFESP]; Miranda-Ferreira, Regiane [UNIFESP]; Smaili, Soraya Soubhi [UNIFESP]; Godinho, Rosely Oliveira [UNIFESP]; los Rios, Cristobal de; Leon, Rafael; Villaroya, Mercedes; Samadi, Abdelouahid; Marco-Contelles, Jose; Jurkiewicz, Neide Hyppolito [UNIFESP]; Garcia, Antonio G.; Jurkiewicz, Aron [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Autonoma Madrid; Hosp Univ Princesa; CSIC; Univ CambridgeWe have recently synthesized a new series of hybrid compounds having the moieties of tacrine, a potent inhibitor of brain and peripheral acetylcholinesterase (AChE), and nimodipine, a blocker of L-type voltage-dependent calcium channels (VDCCs). These compounds were designed to target AChE and L calcium channels in the brain, as potential therapeutic agents in Alzheimer's disease. We performed the present study to determine the main peripheral side effects of two of these compounds, ITH12117 and ITH12118. We have here shown that in rat vas deferens these compounds inhibited AChE with a potency about 1000-fold lower than that of physostigmine or tacrine. Furthermore, the hybrid compounds enhanced contractions evoked by acetylcholine, with a potency about 100-fold lower than that of physostigmine or tacrine. Additionally, contractions induced by Ca2+ on depolarized vas deferens were blocked by nimodipine with greater efficacy, compared with ITH12117 and ITH12118. Compound ITH12118 (1 mu M) caused a pronounced inhibition of the tonic (but not phasic) contraction elicited by electrical field stimulation. Furthermore, the same dose of nimodipine and ITH12118 blocked by 75% cytosolic Ca2+ elevations produced by acetylcholine, noradrenaline, or ATP. As a matter of comparison, we showed that rat brain cortex AChE was inhibited by ITH12118 with a potency 10 to 20-fold higher than that for vas deferens. This study shows that ITH12118 could be a paradigmatic multitarget compound having selective brain effects with smaller peripheral side effects. This may help to orient the search of new neuroprotective compounds with potential therapeutic application in Alzheimer's disease. (C) 2011 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosFunctional antagonism of amphetamine versus ethanol on adrenergic neurotransmission in vas deferens of adolescent rats(Elsevier B.V., 2012-01-15) Silva Junior, Edilson Dantas [UNIFESP]; Caricati-Neto, Afonso [UNIFESP]; Jurkiewicz, Neide Hyppolito [UNIFESP]; Jurkiewicz, Aron [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Because of the few studies that emphasize the in vivo use of amphetamine and ethanol, and their consequences on autonomic neurotransmission, we decided to study the effect of these drugs on peripheral noradrenergic neurotransmission of young animals. We used contractions of the vas deferens of adolescent rats as a model for the study of pre-treatment with both agents. the 30 to 40 day old adolescent rats were pre-treated with amphetamine, at doses of 3 mg/kg, or ethanol at doses of 1.2 g/kg. Both agents were also used simultaneously to investigate possible interactions. the group treated with amphetamine showed a potentiation of the vas deferens contractions evoked by noradrenaline and barium (about 20%), as well as time-response contractions of calcium (about 20%). However, the response to electrical field stimulation (EFS) was not significantly changed, but the content of noradrenaline was reduced by about 50%. the group treated with ethanol showed a decrease in vas deferens contractility to noradrenaline, phenylephrine, and barium, by less than 20%. in this group, contraction by EFS was reduced by about 40% (Tonic, 2 Hz) and 20% (Phasic, 5 Hz), but the response to calcium was not changed. As after amphetamine, the content of noradrenaline was reduced by about 50%. in the group treated with amphetamine + ethanol all the changes described after the single treatments with amphetamine or ethanol were neutralized. It is concluded that a functional antagonism was shown between amphetamine and ethanol when administered simultaneously on peripheral sympathetic neurotransmission in vas deferens of adolescent animals. (C) 2011 Elsevier B.V. All rights reserved.