Navegando por Palavras-chave "inositol phosphate"

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    Aliphatic amino acids in helix VI of the AT(1) receptor play a relevant role in agonist binding and activity
    (Elsevier B.V., 2002-06-15) Corrêa, Silvana Aparecida Alves [UNIFESP]; Zalcberg, H.; Han, S. W.; Oliveira, L.; Costa-Neto, C. M.; Paiva, ACM; Shimuta, S. I.; Universidade Federal de São Paulo (UNIFESP)
    Angiotensin II (AII) AT(1) receptor mutants with replacements of aliphatic amino acids in the distal region of helix VI and the adjoining region of the third extracellular loop (EC-3) were expressed in Chinese hamster ovary (CHO) cells to determine their role in ligand binding and activation. the triple mutant [L262D, L265D, L268D]AT(1) (L3D) showed a marked reduction in affinity for All and for non-peptide (losartan) and peptide ([Sar(1)Leu(8)]All) antagonists; in functional assays using inositol phosphate (IP) accumulation, the relative potency and the maximum effect of All were reduced in L3D. Replacement of Leu(268) (in EC-3) and Leu(262) (in the transmembrane domain) by aspartyl residues did not cause significant changes in the receptor's affinity for the ligands and in IP production. in contrast, the point mutation L265D, at helix VI, markedly decreased affinity and ability to stimulate phosphatidylinositol turnover. Molecular modeling of the AT(1) receptor based on a recent crystal structure of rhodopsin, suggests that the side chain of Leu(265) but not that of Leu(262) is facing a cleft between helices V and VI and interacts with the lipid bilayer, thus helping to stabilize the receptor structure near the Lys(199) residue of helix V in the agonist binding site which is necessary for full activity. (C) 2002 Elsevier Science B.V. All rights reserved.
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    Angiotensin receptor in the heart of Bothrops jararaca snake
    (Elsevier B.V., 2001-04-06) Breno, M. C.; Porto, C. S.; Picarelli, Z. P.; Universidade Federal de São Paulo (UNIFESP); Inst Butantan
    Angiotensin II interacts with specific cell surface angiotensin AT(1) and AT(2) receptors and, in some vertebrates, with an atypical angiotensin AT receptor. This study was designed to characterize the angiotensin receptor in the heart of Bothrops jararaca snake. A specific and saturable angiotensin II binding site was detected in cardiac membranes and yielded K-d = 7.34 +/- 1.41 nM and B-max = 72.49 +/- 18 fmol/mg protein. Competition-binding studies showed an angiotensin receptor with low affinity to both angiotensin receptor antagonists, losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole) and PD123319 ((s)-1-(4-[dimethylamino]-3-methylphenyl)methyl-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylate). Studies on the intracellular signaling pathways showed that phospholipase C/inositol phosphate breakdown and adenylylcyclase/cyclic AMP generation were not coupled with this angiotensin receptor. An adenylylcyclase enzyme sensitive to forskolin was detected. the results indicate the presence of an angiotensin receptor in the heart of B. jararaca snake pharmacologically distinct from angiotensin AT(1) and AT(2) receptors. It seems to belong to a new class of angiotensin receptors, like some other atypical angiotensin AT receptors that have already been described. (C) 2001 Elsevier Science B.V. All rights reserved.
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    Effect of estrogen on intracellular signaling pathways linked to activation of M-2- and M-3-muscarinic acetylcholine receptors in the rat myometrium
    (Elsevier B.V., 2000-02-25) Abdalla, Fernando M. F.; Abreu, Lygia C. [UNIFESP]; Porto, Catarina S. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Inst Butantan
    The estrogen treatment of adult female rats induces an increase in myometrium sensitivity to cholinergic agonists and in this tissue the presence of M-2- and M-3-muscarinic acetylcholine (mACh) receptor was shown. We now report the effect of estrogen on intracellular signaling pathways linked to activation of M-2- and M-3-mACh receptor subtypes. the intracellular cyclic AMP accumulation and [H-3]-inositol phosphates content were measured in myometrium strips from rats in estrus (control) and estradiol-treated rats (12.5 mu g/100 g body weight, sc, 24 h before experiments) (the plasma estradiol level was 30.9 +/- 3.5 pg/ml and 119.3 +/- 14.1 pg/ml from control and estrogen-treated rats, respectively). Estrogen treatment increased 2.5-fold the intracellular cyclic AMP accumulation induced by 10 mu M forskolin. the effects of muscarinic agonist and antagonists on cyclic AMP accumulation were tested. Carbachol reduced the forskolin-induced intracellular cyclic AMP content, 3.0 and 10.5-fold, in myometrium from control and estradiol-treated rats, respectively. This inhibitory effect failed to occur when carbachol was incubated in the presence of methoctramine. Carbachol also induced increase on total [H-3]-inositol phosphates accumulation in myometrium from estradiol-treated rats when compared with control rats. This effect was reversed by pfHHSiD. These studies suggest the modulation by estrogen of intracellular signaling pathways linked to activation of M-2- and M-3-mACh receptors in the rat myometrium. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
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    Effects of estrogen on intracellular signaling pathways linked to activation of muscarinic acetylcholine receptors and on acetylcholinesterase activity in rat hippocampus
    (Elsevier B.V., 2008-05-01) Santos Pereira, Renato Tavares dos; Porto, Catarina Segreti [UNIFESP]; Godinho, Rosely Oliveira [UNIFESP]; Francis Abdalla, Fernando Mauricio; Inst Butantan; Universidade Federal de São Paulo (UNIFESP)
    The aim of the present study was to investigate the effects of estrogen lack and estrogen replacement on the production of total [H-3]inositol phosphate ([H-3]IP) induced by the activation of muscarinic acetylcholine receptors (mAChRs) and on the mechanisms for inactivation of acetylcholine. Hippocampi were obtained from rats in proestrus (PE), ovariectomized for 15 days (C15), ovariectomized for 15 days and then treated with 17 beta-estradiol for 7 days (E7) and ovariectomized and immediately treated with 17 beta-estradiol for 21 days (E21). Ovariectomy did not change the basal level of total [H-3]IP in the hippocampus. 17 beta-Estradiol replacement (E7 and E21) reduced the basal level of total [H-3]IP. in all experimental groups, carbachol (CCh) caused a concentration -dependent rise in total [H-3]IP. the maximum effect was reached with 10(-4) M CCh. the response to 10(-4) M CCh in the hippocampi from C15 and E7 rats was twofold higher than in hippocampi from PE and E21 animals and was blocked by pirenzepine, but not by methoctramine. Ovariectomy or 17 beta-estradiol treatment for 7 days did not change neither the total acetylcholinesterase (AChE) activity nor the relative amount of mono- and dimeric G(1)/G(2) and tetrameric G(4) globular forms. Conversely, hormonal treatment for 21 days induced an increase in AChE activity of G(1)/G(2) and G(4) forms, indicating that 17 beta-estradiol stimulates both synthesis and assembly of AChE molecular forms. the present results suggest that the duration and/or a critical period with regard to the initiation of estrogen therapy are important to regulate the function of mAChRs and AChE activity in female rat hippocampus. (C) 2008 Elsevier Inc. All rights reserved.