RESUMO
The use of clonidine, a selective agonist of α2-adrenoceptors, is related to the fertility impairment. Thus, it has been described that changes in the epididymal function are related to the loss of fertility. Therefore, this study was sought to further evaluate the effects of clonidine in the rat distal cauda epididymis contractions and its consequence in the sperm parameters. The in vitro effects of clonidine in the isolated distal cauda epididymis were evaluated by pharmacological experiments. The consecutive contractile responses for clonidine in distal cauda epididymis showed desensitization. The noradrenaline-induced contractions were desensitized after in vitro clonidine pre-treatment (10(-5) M for 10 min). Clonidine was unable to alter the noradrenaline contractions if the in vitro pre-treatment was made in the presence of idazoxan (α2-adrenoceptor antagonist), whereas prazosin (α1-adrenoceptor antagonist) was ineffective. Moreover, the in vitro clonidine pre-treatment increased frequency and amplitude of spontaneous contraction of distal cauda epididymis. In addition, to induce in vivo desensitization of α2-adrenoceptors, male Wistar rats were treated with crescent doses of clonidine and distal cauda of epididymis contraction and sperm parameters were analyzed. The in vivo treatment with clonidine diminished the potency of the contractions induced by adrenergic agonists and augmented the frequency and amplitude of spontaneous contraction of distal cauda epididymis. This treatment also altered the sperm transit time in epididymis, epididymal sperm reserves, sperm lipid peroxidation, and antioxidant enzymes activity. The results suggest that clonidine was able to affect the sperm quantity and quality by decreasing the transit time related to the increase in the frequency and amplitude of spontaneous contractions in epididymis, although the contractions induced by adrenergic agonists were desensitized.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Clonidina/farmacologia , Epididimo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Epididimo/fisiologia , Masculino , Contração Muscular/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Carbachol-induced contractions of rat stomach fundus strips, obtained in a nutrient solution containing 1.8 mM Ca2+, were resistant to Ca2+ withdrawal, even after 1 h of bathing the tissues in a nominal 0 Ca2+ solution. This was not observed when K+ was used to evoke contractions, which were rapidly inhibited after Ca2+ removal (t1/2=2 min). The effect of carbachol in 0 Ca2+ solution was reduced by using drugs that reduce intracellular pools of Ca2+, such as caffeine (1-3 mM), ryanodine (30 microM) or thapsigargin (1 microM), corroborating the involvement of intracellular Ca2+ stores. On the other hand, when the 0 Ca2+ solution contained EGTA, a complete decline of carbachol effects was observed within about 8 min, indicating the involvement of extracellular Ca2+. Atomic absorption spectrometry showed that our 0 Ca2+ solution still contained 45 microM Ca2+, which was drastically reduced to 5.9 nM in the presence of EGTA. Taken together, our results indicate that the effects of carbachol are due to the mobilization of caffeine-, ryanodine- and thapsigargin-sensitive intracellular Ca2+ stores, and that these stores are not inactivated or depleted if micromolar concentrations (45 microM), but not nanomolar concentrations (5.9 nM) of Ca2+ are maintained in the extracellular milieu.
Assuntos
Cálcio/metabolismo , Fundo Gástrico/fisiologia , Receptores Muscarínicos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Cafeína/farmacologia , Cálcio/farmacologia , Carbacol/farmacologia , Quelantes/farmacologia , Agonistas Colinérgicos/farmacologia , Ácido Egtázico/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Músculo Liso/fisiologia , Níquel/farmacologia , Peristaltismo/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Ratos , Ratos Endogâmicos WF , Rianodina/farmacologia , Tapsigargina/farmacologiaRESUMO
1. The actions of the alpha1-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could result in self-cancelling actions. 2. Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA2 values of 7.38+/-0.05 (slope=0.98+/-0.03) and 6.78+/-0.14 (slope=1.08+/-0.06), respectively. 3. When the experiments were repeated in the presence of cocaine (6 microM) the potency (pA2) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72+/-0.07 (slope=1.10+/-0.05) while its potency remained unchanged in the aorta (pA2=6.69+/-0.12; slope=1.04+/-0.05). 4. In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79+/-0.07; slope=1.09+/-0.06). 5. It is suggested that indoramin blocks alpha1-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA2 values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pKB values.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1 , Antagonistas Adrenérgicos alfa/farmacologia , Aorta/efeitos dos fármacos , Indoramina/farmacologia , Ducto Deferente/efeitos dos fármacos , Vasoconstritores/farmacologia , Animais , Cocaína/farmacologia , Masculino , Norepinefrina/antagonistas & inibidores , Norepinefrina/farmacologia , Ratos , Ratos WistarRESUMO
The contractile effect of serotonin was studied in rat vas deferens, in comparison with that of noradrenaline and tyramine, after reserpine treatment, surgical denervation, and transplantation to the colon. In reserpinized animals the effect of 5HT resembled that of tyramine, since it was strikingly reduced, in spite of a small residual effect, showing that in normal preparations the effects of 5HT and tyramine are predominantly due to the release of endogenous noradrenaline. However, in denervated or transplanted vas deferens, in which the effect of tyramine is also abolished, the effect of 5HT was potentiated. It is suggested that after chronic, long lasting depletion of endogenous noradrenaline, there are alternate mechanisms that are generated to improve the contractile effect of 5HT, but not of tyramine. The nature of these mechanisms is still unknown.
Assuntos
Contração Muscular/efeitos dos fármacos , Serotonina/farmacologia , Ducto Deferente/efeitos dos fármacos , Inibidores da Captação Adrenérgica/farmacologia , Animais , Denervação , Relação Dose-Resposta a Droga , Masculino , Norepinefrina/farmacologia , Ratos , Ratos Wistar , Reserpina/farmacologia , Simpatomiméticos/farmacologia , Tiramina/farmacologia , Ducto Deferente/lesões , Ducto Deferente/fisiologiaRESUMO
The contractile effect of serotonin was studied in rat vas deferens, in comparison with that of noradrenaline and tyramine, after reserpine treatment, surgical denervation, and transplantation to the colon. In reserpinized animals the effect of 5HT resembled that of tyramine, since it was strikingly reduced, in spite of a small residual effect, showing that in normal preparations the effects of 5HT and tyramine are predominantly due to the release of endogenous noradrenaline. However, in denervated or transplanted vas deferens, in which the effect of tyramine is also abolished, the effect of 5HT was potentiated. It is suggested that after chronic, long lasting depletion of endogenous noradrenaline, there are alternate mechanisms that are generated to improve the contractile effect of 5HT, but not of tyramine. The nature of these mechanisms is still unknown.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Íleo/metabolismo , Modelos Biológicos , Receptores Adrenérgicos alfa/metabolismo , Agonistas alfa-Adrenérgicos/administração & dosagem , Antagonistas Adrenérgicos alfa/administração & dosagem , Animais , Dioxanos , Epinefrina/administração & dosagem , Epinefrina/farmacologia , Cobaias , Íleo/efeitos dos fármacos , Indoramina/administração & dosagem , Indoramina/farmacologia , Contração Muscular/efeitos dos fármacos , Norepinefrina/administração & dosagem , Norepinefrina/farmacologia , Fenilefrina/administração & dosagem , Fenilefrina/farmacologia , Piperoxano/administração & dosagem , Piperoxano/farmacologia , Prazosina/administração & dosagem , Prazosina/farmacologia , Receptores Adrenérgicos alfa/efeitos dos fármacosAssuntos
Mucosa Intestinal/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Ducto Deferente/transplante , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Clonidina/análogos & derivados , Clonidina/farmacologia , Isradipino/farmacologia , Masculino , Contração Muscular/efeitos dos fármacos , Norepinefrina/farmacologia , RatosRESUMO
Experiments were performed with rat vas deferens to verify whether agmatine, an endogenous ligand for adrenoceptors and imidazoline receptors, can influence sympathetic neurotransmission, with respect to contractions induced by transmural nerve stimulation, contractions induced by exogenous noradrenaline, and overflow of endogenous noradrenaline. It was shown that agmatine (a) caused a dose-dependent potentiation of electrically induced twitches, up to about 70% in relation to controls, (b) shifted to the right the inhibitory concentration-response curves for clonidine on electrically induced twitches, indicating competitive antagonism at presynaptic alpha-adrenoceptors, with a pA2 value of 4.12 +/- 0.10, (c) shifted to the right the concentration-response curves for noradrenaline-induced contractions, indicating competitive antagonism at postsynaptic alpha-adrenoceptors as well, with a pA2 value of 4.03 +/- 0.10, and (d) caused a dose-dependent increase of KCI-induced overflow of noradrenaline, up to about 90% in relation to controls. It is concluded that agmatine has multiple effects on sympathetic neurotransmission in rat vas deferens.
Assuntos
Agmatina/farmacologia , Contração Muscular/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Ducto Deferente/efeitos dos fármacos , Animais , Clonidina/farmacologia , Estimulação Elétrica , Técnicas In Vitro , Masculino , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Norepinefrina/metabolismo , Norepinefrina/farmacologia , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa/efeitos dos fármacos , Ducto Deferente/metabolismoAssuntos
Clonidina/farmacologia , Ducto Deferente/efeitos dos fármacos , Animais , Fatores Biológicos/farmacologia , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/ultraestrutura , Feminino , Técnicas In Vitro , Masculino , Microscopia Eletrônica , Contração Muscular/efeitos dos fármacos , Ratos , Ratos Wistar , Útero/efeitos dos fármacos , Ducto Deferente/metabolismo , Ducto Deferente/ultraestruturaRESUMO
Radioligand binding assays were performed with the selective antagonist of dihydropyridine-sensitive Ca2+ channels [3H]PN200-110 (isradipine) in rat vas deferens, before and 7 days after denervation, and data were compared with those obtained for K(+)-induced contractions, which are Ca(2+)-dependent. The density (Bmax) of dihydropyridine binding sites was decreased to almost one-third of its normal value after denervation. The respective affinity (KD) was not significantly changed. In addition, it was observed that the K(+)-induced tonic contraction, which corresponded to 55 +/- 2% of the respective phasic contraction, was decreased to 41 +/- 3% after denervation. It is assumed that the decreased density of Ca2+ channels causes a decrease in K(+)-induced influx of Ca2+ and consequently of the corresponding tonic contraction. These results indicate that autonomic innervation can regulate the density of dihydropyridine-sensitive Ca2+ channels in the rat vas deferens.