952 resultados para [alpha]2-macroglobulin


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Central cholinergic activation by pilocarpine induces salivation dependent on the integrity of forebrain areas. The present work investigates the autonomic mediation of this salivation. Pilocarpine (500 nmol/rat) was injected into the lateral ventricle (LV) of tribromoethanol-anesthetized adult male rats. Preweighed cotton balls were inserted into the oral cavity and weighed again 7 min later. ol-adrenoceptor antagonists (3-50 mu mol/kg) prazosin (alpha(1)), yohimbine (alpha(2)) or propranolol (beta) injected intraperitoneally (i.p.) produced, 80%, 20% and 0% inhibition respectively of the LV pilocarpine-induced salivation. Intracerebroventricular injections (160 nmol) of the antagonists did not alter the effects of pilocarpine injected into the LV. Bilateral section of chorda tympani nerve or bilateral sympathetic cervical ganglionectomy produced 0% and 40% inhibition of pilocarpine-induced salivation, respectively. Ganglionectomy did not alter salivation induced by i.p, injection of pilocarpine (4 mu mol/kg). The results indicate that there is a large sympathetic contribution to the salivation induced by central cholinergic activation. (C) 1999 Elsevier B.V. B.V. All rights reserved.

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We determined the effects of moxonidine and rilmenidine 20 mol (alpha(2)-adrenergic and imidazoline receptor agonists) injected into the medial septal area (MSA) on the pilocarpine-induced salivation, when injected intraperitoneally (i.p.), of male Holtzman rats weighing 250300 g, with stainless-steel cannula implanted into the MSA. The rats were anesthetized with zoletil 50 mg kg(-1) b.wt. (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle intramuscularly (IM), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The pre-treatment with moxonidine injected into the MSA reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (12 +/- 3 mg min(-1)) vs. control (99 +/- 9 mg min(-1)). The pre-treatment with rilmenidine 40 nmol also reduced the salivation induce by pilocarpine injected i.p. (20 +/- 5 mg min(-1)) vs. control (94 +/- 7 mg min(-1)). Idazoxan 40 nmol (imidazoline receptor antagonist) injected into the MSA previous to moxonidine and rilmenidine partially blocked the effect of moxonidine and totally blocked the rilmenidine effect in pilocarpine-induced salivation injected i.p. (60 +/- 8 and 95 +/- 10 mg min(-1), respectively). Yohimbine 40 nmol (alpha(2)-adrenergic receptor antagonist) injected into the MSA previously to moxonidine and rilmenidine partially blocked the moxonidine effect but produced no change on the rilmenidine effect on i.p. pilocarpine-induced salivation (70 +/- 6 and 24 +/- 6 mg min(-1), respectively). Injection of these alpha(2)-adrenergic and imidazoline agonists and antagonists agents i.p. produced no change on i.p. pilocarpine-induced salivation. These results show that central, but not peripheral, injection of alpha(2)-adrenergic and imidazoline agonists' agents inhibit pilocarpine-induced salivation. Idazoxan, an imidazoline receptor antagonist, totally inhibits the rilmenidine effect and partially inhibits the moxonidine effect on pilocarpine-induced salivation. Yohimbine produced no change on rilmenidine effect but partially inhibited the moxonidine effect. Both of these antagonists when injected into the MSA previous to pilocarpine i.p. potentiated the sialogogue effect of pilocarpine. The results suggest that alpha(2)-adrenergic/imidazoline receptor of the MSA when stimulated blocked pilocarpine-induced salivation in rats when injected intraperitonially These receptors of the medial septal area have an inhibitory mechanism on salivary secretion. (C) 2004 Elsevier B.V. All rights reserved.

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In the present study, we investigated the effects of pretreatment with N-G-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor) injected intravenously (IV) on the hypotension, bradycardia, and vasodilation produced by moxonidine (alpha(2)-adrenergic/imidazoline receptor agonist) injected into the fourth brain ventricle (4th V) in rats submitted to acute hypertension that results from baroreflex blockade by bilateral injections of kynurenic acid (kyn, glutamatergic receptor antagonist) into the nucleus of the solitary tract (NTS) or in normotensive rats. Male Wistar rats (n = 5 to 7/group) anesthetized with IV urethane (1.0 g kg(-1) of body weight) and a-chloralose (60mg kg(-1) of body weight) were used. Bilateral injections of kyn (2.7 nmol 100 nL(-1)) into the NTS increased baseline mean arterial pressure (148 +/- 11 mm Hg, vs. control: 102 +/- 4mm Hg) and baseline heart rate (417 +/- 11 bpm, vs. control: 379 +/- 6 bpm). Moxonidine (20 nmol mu L-1) into the 4th V reduced mean arterial pressure and heart rate to similar levels in rats treated with kyn into the NTS (68 +/- 9 mm Hg and 359 +/- 7 bpm) or in control normotensive rats (66 +/- 7 mm Hg and 362 +/- 8 bpm, respectively). The pretreatment with L-NAME (2 5 mu mol kg-1, IV) attenuated the hypotension produced by moxonidine into the 4th V in rats treated with kyn (104 +/- 6 mm Hg) or in normotensive rats (95 +/- 8 mm Hg), without changing bradycardia. Moxonidine into the 4th V also reduced renal, mesenteric, and hindquarter vascular resistances in rats treated or not with kyn into the NTS and the pretreatment with L-NAME IV reduced these effects of moxonidine. Therefore, these data indicate that nitric oxide mechanisms are involved in hypotension and mesenteric, renal, and hindquarter vasodilation induced by central moxonidine in normotensive and in acute hypertensive rats.

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Cholinergic, agonists activate salivation and the alpha (2)-adrenergic and imidazoline receptor agonists induce opposite effects. In the present study, we investigated the effects of intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of moxonidine (an a-adrenergic and imidazoline receptor agonist) on the salivation induced by the cholinergic agonist pilocarpine. Male Holtzman rats wish stainless steel cannula implanted into the lateral ventricle (LV) were used. In rats anesthetized with tribromoethanol (200 mg kg(-1)), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The treatment with moxonidine (5, 10 and 20 nmol in 1 mul) injected,i.c.v. reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (48 +/- 5, 17 +/- 2 and 15 +/- 2 mg min(-1) vs. control, 73 +/- 7 mg min(-1)). The same doses of moxonidine injected i.c.v. also reduced the salivary secretion induced by pilocarpine (500 nmol in 1 mul). injected i.c.v. (44 +/- 1, 14 +/- 2 and 20 +/- 3 mg min(-1) vs. control, 51 +/- 2 mg min(-1)). Injection of moxonidine (20 nmol in 0.1 ml) i.p. produced no chance on i.p. pilocarpine-induced salivation (58 +/- 4 mg min(-1) vs. control, 50 +/- 4 mg min(-1)). The results show that central, but not peripheral, injection of moxonidine inhibit,. pilocarpine-induced salivation, suggesting that central mechanisms activated by alpha (2)-adrenergic/imidazoline agonists inhibit cholinergic-induced salivation in rats. (C) 2001 Elsevier B.V. B.V. All rights reserved.

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The aim of the present study was to analyze the role of alpha(1),alpha(2)-adrenoceptors, and the effects of losartan and PD123319 (selective ligands of the AT(1) and AT(2) angiotensin receptors, respectively) injected into the paraventricular nucleus (PVN) on the diuresis, natriuresis, and kaliuresis induced by administration of adrenaline into the medial septal area (MSA). Male Holtzman rats with a stainless steel cannula implanted into the MSA and bilaterally into the PVN were used. The administration of adrenaline into the MSA increased in a dose-dependent manner the urine, sodium, and potassium excretions. The previous administration of prazosin (an alpha(1)-adrenoceptor antagonist) injected into the PVN abolished the above effects of adrenaline, whereas yohimbine (an a-adrenoceptor antagonist) doesn't affect the diuresis, natriuresis, and kaliuresis induced by adrenaline. Pretreatment with losartan into the PVN decreased in a dose-dependent manner the urine, sodium, and potassium excretions induced by MSA administration of adrenaline (50 ng), while PVN PD123319 was without effect. These results indicate that urinary and electrolyte excretion effects induced by adrenaline into the MSA are mediated primarily by PVN AT, receptors. However, the doses of losartan were more effective when combined with the doses of PD123319 than given alone, suggesting that the urinary, natriuretic, and kaliuretic effects of MSA adrenaline may involve activation of multiple angiotensin II receptors subtypes into the PVN. (C) 2004 Elsevier B.V All rights reserved.

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Peripheral treatment with the cholinergic agonist pilocarpine induces intense salivation that is inhibited by central injections of the alpha(2)-adrenergic/imidazoline receptor agonist moxonidine. Salivary gland blood flow controlled by sympathetic and parasympathetic systems may affect salivation. We investigated the changes in mean arterial pressure (MAP) and in the vascular resistance in the submandibular/sublingual gland (SSG) artery, superior mesenteric (SM) artery and low abdominal aorta (hindlimb) in rats treated with intraperitoneal (i.p.) pilocarpine alone or combined with intracerebroventricular (i.c.v.) moxonidine. Male Holtzman rats with stainless steel cannula. implanted into lateral ventricle (LV) and anesthetized with urethane were used. Pilocarpine (4 mumol/kg of body weight) i.p. reduced SSG vascular resistance (-50 +/- 13% vs. vehicle: 5 +/- 3%). Pilocarpine i.p. also increased mesenteric vascular resistance (15 +/- 5% vs. vehicle: 2 +/- 3%) and MAP (16 +/- 3 mmHg, vs. vehicle: 2 +/- 3 mmHg). Moxonidine (20 nmol) i.c.v. increased SSG vascular resistance (88 +/- 12% vs. vehicle: 7 +/- 4%). When injected 15 min following i.c.v. moxonidine, pilocarpine i.p. produced no change on SSG vascular resistance. Pilocarpine-induced pressor responses and increase in mesenteric vascular resistance were not modified by i.c.v. moxonidine. The treatments produced no change in heart rate (HR) and hindlimb vascular resistance. The results show that (1) i.p. pilocarpine increases mesenteric vascular resistance and MAP and reduces salivary gland vascular resistance and (2) central moxonidine increases salivary gland vascular resistance and impairs pilocarpine-induced salivary gland vasodilatation. Therefore, the increase in salivary gland vascular resistance may play a role in the anti-salivatory response to central moxonidine. (C) 2003 Elsevier B.V. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Afferents to the primary startle circuit are essential for the elicitation and modulation of the acoustic startle reflex (ASR). In the rat, cochlear root neurons (CRNs) comprise the first component of the acoustic startle circuit and play a crucial role in mediating the ASR. Nevertheless, the neurochemical pattern of their afferents remains unclear. To determine the distribution of excitatory and inhibitory inputs, we used confocal microscopy to analyze the immunostaining for vesicular glutamate and GABA transporter proteins (VGLUT1 and VGAT) on retrogradely labeled CRNs. We also used reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry to detect and localize specific neurotransmitter receptor subunits in the cochlear root. Our results show differential distributions of VGLUT1- and VGAT-immunoreactive endings around cell bodies and dendrites. The RT-PCR data showed a positive band for several ionotropic glutamate receptor subunits, M1-M5 muscarinic receptor subtypes, the glycine receptor alpha 1 subunit (GlyR alpha 1), GABA(A), GABA(B), and subunits of alpha 2 and beta-noradrenergic receptors. By immunohistochemistry, we confirmed that CRN cell bodies exhibit positive immunoreaction for the glutamate receptor (GluR) 3 and NR1 GluR subunits. Cell bodies and dendrites were also positive for M2 and M4, and GlyR alpha 1. Other subunits, such as GluR1 and GluR4 of the AMPA GluRs, were observed in glial cells neighboring unlabeled CRN cell bodies. We further confirmed the existence of nor-adrenergic afferents onto CRNs from the locus coeruleus by combining tyrosine hydroxylase immunohistochemistry and tract-tracing experiments. Our results provide valuable information toward understanding how CRNs might integrate excitatory and inhibitory inputs, and hence how they could elicit and modulate the ASR. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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ADP-glucose pyrophosphorylase is the key regulatory enzyme in the biosynthesis of starch in plants and glycogen in bacteria. The enzyme from potato tuber is comprised of a regulatory subunit and a catalytic subunit and is present as a heterotetramer (alpha(2)beta(2)) the catalytic subunit from potato tuber (50 kDa) was crystallized in four different forms, two of which are suitable for structural studies. A tetragonal crystal form obtained in the presence of the substrate analog Cr-ATP diffracted to 2.2 Angstrom and belongs to space group P4(1) (or its enantiomorph), with unit-cell parameters a = b = 110.57, c = 190.14 Angstrom. A second crystal form obtained diffracted to 2.8 Angstrom and belongs to space group PZ, with unit-eel parameters a = 80.06, b = 138.84, c = 92.20 Angstrom, beta = 112.40 degrees. As this protein displays no significant homology to any currently known protein structure, a search for heavy-atom derivatives has been initiated.

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Critical limits of a stationary nonlinear three-dimensional Schrodinger equation with confining power-law potentials (similar to r(alpha)) are obtained using spherical symmetry. When the nonlinearity is given by an attractive two-body interaction (negative cubic term), it is shown how the maximum number of particles N-c in the trap increases as alpha decreases. With a negative cubic and positive quintic terms we study a first order phase transition, that occurs if the strength g(3) of the quintic term is less than a critical value g(3c). At the phase transition, the behavior of g(3c) with respect to alpha is given by g(3c)similar to 0.0036+0.0251/alpha+0.0088/alpha(2).

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)