RESUMO
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.
Assuntos
Isradipino/metabolismo , Ducto Deferente/metabolismo , Animais , Sítios de Ligação/efeitos dos fármacos , Canais de Cálcio/efeitos dos fármacos , Denervação , Di-Hidropiridinas/farmacologia , Masculino , Contração Muscular/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Ratos , Ratos Wistar , Ducto Deferente/efeitos dos fármacosRESUMO
The mechanisms that regulate programmed cell death, such as apoptosis, and the cellular "self-eating" phenomenon of autophagy, share many regulatory systems and common pathways. These mechanisms have been extensively investigated over the last few years. Some intracellular structures may determine and control the autophagic fate of the cell such as the endoplasmic reticulum, mitochondria, and lysosomes. The coordination and interrelation of these organelles are crucial in maintaining calcium levels and general cellular homeostasis, as well as in regulating cell life and death under physiological and pathological conditions, including cancer, neurodegeneration, and aging. In this review, we discuss the crosstalk between the aforementioned organelles and their influence in apoptotic and autophagic processes.
Assuntos
Envelhecimento/genética , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Envelhecimento/metabolismo , Animais , Apoptose/genética , Autofagia/genética , Retículo Endoplasmático/genética , Regulação da Expressão Gênica , Homeostase , Humanos , Lisossomos/genética , Mitocôndrias/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Transdução de SinaisRESUMO
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.