Search results for "serpin"

Estudio conductual, electrofisiológico e inmunohistoquímico del modelo de fibromialgia inducido por reserpina en rata

2016

El síndrome de fibromialgia (FMS) es una patología de etiología desconocida caracterizada por dolor musculoesquelético generalizado acompañado de otros síntomas entre los que destacan las alteraciones del sueño y los trastornos depresivos, que afecta gravemente a la calidad de vida de los pacientes. Tiene una prevalencia relativamente importante en nuestra sociedad lo que determina que tenga un elevado impacto socio-económico. El desconocimiento de la causa que la genera y los recientes cambios en los criterios diagnósticos contribuyen a que, a pesar de los avances, actualmente el tratamiento del FMS no consiga alcanzar un grado de eficacia suficientemente satisfactorio. Es necesario el est…

�ber den Wirkungsmechanismus von Reserpin

1959

Evaluation of PAI-1 in endometriosis using a homologous immunocompetent mouse model

2018

To analyze the role of PAI-1 (plasminogen activator inhibitor 1) in endometriotic lesion growth, we studied the effect of PAI-1 inhibition by PAI-039 using a homologous mouse model of endometriosis that allows noninvasive monitoring. Endometrial tissue from donor mice was collected, labeled with mCherry adenovirus, and implanted into a subcutaneous pocket on the ventral abdomen of recipient mice. Seven days after transplantation, mice were randomly allocated in two groups and treated once daily for 2 weeks with either vehicle (control group) or PAI-1 inhibitor (PAI-039 group). Endometriotic lesion size generated in recipient mice was monitored by mCherry signal. Animals were euthanized 21 d…

Inactivation and polymerization of human neuroserpin

2010

Neuroserpin is an inhibitory enzyme, belonging to the family of serpins and involved in several pathologies, such as ischemia, Alzheimer disease, and FENIB (Familial Encephalopathy with Neuroserpin Inclusion Body). Here, we study the mechanism of neuroserpin inactivation and polymerization by different experimental techniques (static and dynamic light scattering, liquid chromatography, Fourier transform infrared spectroscopy, emission spectroscopy). Our results show that at intermediate temperatures (45-55 °C) neuroserpin forms flexible polymers with a size from a few tens to a few hundreds of nanometers. At high temperatures, above 80 °C, our results reveal a different polymeric form, reac…

Functional and dysfunctional isoforms of human neuroserpin

2015

Neuroserpin (NS) is a serine protease inhibitor (SERPIN) involved in different neurological pathologies, including the Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB), related to the aberrant polymerization of NS mutants. Here we present an in vitro and in silico characterization of native NS and its dysfunctional conformation isoforms: the proteolytically cleaved conformer, the inactive latent conformer, and the polymeric conformer. Using circular dichroism and fluorescence spectroscopy, we present an experimental validation of the latent model and highlight the main structural features of the different conformers. In par- ticular, emission spectra of aromatic residues yi…

Characteristics of histamine tachyphylaxis in rat uterine smooth muscle.

2002

Objective and design: To study both the desensitisation induced by short-term exposure to histamine and the mechanism responsible in the isolated rat uterus.¶Material: Precontracted isolated uterus (37 mM KCl) from oestrogenised Wistar rats were used.¶Treatment: Repetitive responses to histamine (10–6, 10–5, 10–4, 10–3 M), dimaprit and clonidine (10–4 M) were tested at 15, 30, 45 and 105 min., with their modifications by (5 mg/ kg, 24 h before sacrifice) reserpine, 10–7 M propranolol, 10–8 M atropine, and 10–6 M indomethacin. Dose-response curves for adrenaline were carried out as standard protocol.¶Methods: In vitro techniques (de Jalon's solution, 31°C, carbogen, isotonic registration, re…

Neuronal and extraneuronal uptake and efflux of catecholamines in the isolated rabbit heart

1974

1. Isolated rabbit hearts were perfused with (−)-noradrenaline, (−)-adrenaline and (±)-isoprenaline for various time periods (1–180 min) and then washed with an amine-free medium. The venous concentration of the amine was estimated fluorimetrically during the infusion and after its end, to study removal and efflux, respectively. 2. In untreated hearts and after pretreatment with reserpine the removal had a constant rate over 20–60 min. After pretreatment with pargyline to block monoamine oxidase (MAO), however, the removal of noradrenaline declined exponentially to zero. Inhibition of the neuronal uptake (desipramine) and chemical sympathectomy (6-hydroxydopamine) abolished the removal of n…

The neuronal efflux of noradrenaline: Dependency on sodium and facilitation by ouabain

1974

Rabbit hearts were isolated after pretreatment with the MAO inhibitor pargyline and with reserpine and were perfused with 200 ng/ml noradrenaline for 1 h. During the subsequent wash-out with an amine-free solution for 2 h, the neuronal efflux of noradrenaline declined mono-exponentially with a mean halftime of 42 min. Both Na+-free solution and ouabain caused facilitation of the efflux which thereafter declined in a multi-exponential fashion. The maximum facilitation was reached after 3 min of Na+-free perfusion and 25 min after introduction of ouabain. The amount of exogenous noradrenaline accumulated in the heart was only partially released when the extracellular Na+-concentration was nor…

RELEASE OF CATECHOLAMINES FROM THE HEART

1966

Publisher Summary This chapter discusses the release of catecholamines from the heart. The isolated heart of the rabbit with the sympathetic nervous supply from the right stellate ganglion intact was set up according to Hukovio and Muscholl. The ganglion was stimulated for 30 s at supramaximal voltage with rectangular impulses of 3–5 ms duration a frequency of 10 shocks/s. Each stimulation period was followed by a resting period of 30 s. In the rabbit, four doses of 50 mg/kg l-α-methyldopa decreased the noradrenaline concentration in auricles, right, and left ventricles by 38–60%. An equimolar amount of α-methyl noradrenaline was detected in the tissues. Reserpine and guanethidine in doses,…

Relaxant effect of dopamine on the isolated rat uterus.

1988

The effect of dopamine was studied on the isolated uterus of diethylstilboestrol-treated rats. Dopamine, at concentrations (10(7)-10(-4) M) produced a concentration-dependent relaxation in the K+-depolarized rat uterus. On a molar basis, dopamine was about 500 times less potent than adrenaline in relaxing the uterus, the maximum degree of relaxation obtained with both drugs was the same. Pretreatment of the rats with reserpine (5 mg/kg) did not produce any modification of the dose-response curve to dopamine. Similarly, cocaine (3 x 10(-6) M) failed to modify the relaxant effect of dopamine. The dopamine induced relaxation was inhibited by propranolol (10(-9)-10(-7) M) in a dose-dependent ma…