Navegando por Palavras-chave "nicotinic receptor"
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- ItemSomente MetadadadosBlockade by agmatine of catecholamine release from chromaffin cells is unrelated to imidazoline receptors(Elsevier B.V., 2001-04-06) Santos, W. C.; Hernandez-Guijo, J. M.; Ruiz-Nuno, A.; Olivares, R.; Jurkiewicz, A.; Gandia, L.; Garcia, A. G.; Univ Autonoma Madrid; Universidade Federal de São Paulo (UNIFESP); Univ Amazonas; Hosp PrincesaThe blockade of exocytosis induced by the putative endogenous ligand for imidazoline receptors, agmatine, was studied by using on-line measurement of catecholamine release in bovine adrenal medullary chromaffin cells. Agmatine inhibited the acetylcholine-evoked release of catecholamines in a concentration-dependent manner (IC50 = 366 muM); the K+-evoked release of catecholamines was unaffected. Clonidine (100 muM) and moxonidine (100 muM) also inhibited by 75% and 50%, respectively, the acetylcholine-evoked response. in cells voltage-clamped at -80 mV, the intermittent application of acetylcholine pulses elicited whole-cell inward currents (I-ACh) that were blocked 63% by 1 mM agmatine. the onset of blockade was very fast (tau (on) = 31 ms); the recovery of the current after washout of agmatine also occurred very rapidly (tau (off) = 39 ms). Efaroxan (10 muM) did not affect the inhibition of I-ACh elicited by 1 mM agmatine. I-ACh was blocked 90% by 100 muM clonidine and 50% by 100 muM moxonidine. the concentration-response curve for acetylcholine to elicit inward currents was shifted to the right in a non-parallel manner by 300 muM agmatine. the blockade of I-ACh caused by agmatine (100 muM) was similar at various holding potentials, around 50%. When intracellularly applied, agmatine did not block I-ACh. At 1 mM, agmatine blocked I-Na by 23%, I-Ba by 14%, I-K(Ca) by 16%, and I-K(VD) by 18%. in conclusion, agmatine blocks exocytosis in chromaffin cells by blocking nicotinic acetylcholine receptor currents. in contrast to previous views, these effects seem to be unrelated to imidazoline receptors. (C) 2001 Elsevier Science B.V. All rights reserved.
- ItemSomente MetadadadosMechanism of neuromuscular blockade induced by phenthonium, a quaternary derivative of (-)-hyoscyamine, in skeletal muscles(Stockton Press, 1998-07-01) Souccar, Caden [UNIFESP]; Lima-Landman, MTR; Ballejo, G.; Lapa, Antonio José [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)1 the mechanisms underlying the postjunctional blockade induced by phenthonium [N-(4-phenyl) phenacyl 1-hyoscyamine] were investigated in mammalian and amphibian muscles. This muscarinic antagonist was previously shown to enhance specifically the spontaneous acetylcholine (ACh) release at concentrations that blocked neuromuscular transmission.2 in both rat diaphragm and frog sartorius muscles, phenthonium (Phen, 1-100 mu M) depressed the muscle twitches elicited by nerve stimulation (IC50: 23 mu M and 5 mu M, respectively), and blocked the nerve-evoked muscle action potential. the neuromuscular blockade was not reversed after incubation with neostigmine.3 Equal concentrations of Phen decreased the rate of rise and prolonged the falling phase of the directly elicited action potential in frog sartorius muscle fibres, indicating that the drug also affects the sodium and potassium conductance.4 Phen (50 and 100 mu M) protected the ACh receptor against alpha-bungarotoxin (BUTX) blockade in the mouse diaphragm allowing recording of endplate potentials and action potentials after 5 h wash with physiological salt solution.5 Phen (10-100 mu M) produced a concentration- and voltage-dependent decrease of the endplate current (e.p.c.), and induced nonlinearity of the current-voltage relationship. At high concentrations Phen also shortened the decay time constant of e.p.c (tau(e.p.c.)) and reduced its voltage sensitivity.6 At the same range of concentrations, Phen also reduced the initial rate of [I-125]-BUTX binding to junctional ACh receptors of the rat diaphragm (apparent dissociation constant = 24 mu M), the relationship between the degree of inhibition and antagonist concentration being that expected for a competitive mechanism.7 It is concluded that Phen affects the electrical excitability of the muscle fibre membrane, and blocks neuromuscular transmission through a mechanism that affects the agonist binding to its recognition site and ionic channel conductance of the nicotinic ACh receptor.
- ItemSomente MetadadadosNicotinic receptor/ionic channel complex (AChR) in androgen-dependent skeletal muscle cultures(Springer, 2002-02-01) Bielavsky, M.; Souccar, C.; Lapa, A. J.; Lima-Landman, MTR; Universidade Federal de São Paulo (UNIFESP)The kinetic properties of the nicotinic receptor/ionic channel complex (AChR) were compared in cell cultures obtained from androgen-dependent skeletal muscles of the perineal complex (P) and from muscles less dependent upon sex hormones (the thigh musculature, T). Because the development of P is delayed compared to other skeletal muscles in the rat, cultures were performed taking into account the age of the donor (4- or 6-day-old rats), and the time interval the cells remained in culture (7 days and 15 days). the ionic channel conductance (gamma) and the mean channel open time (2) were determined with the patch-clamp technique in the cell-attached configuration at room temperature. Cultures from P and T muscles were morphologically identical in size and shape, independent of the animals' age at plating or on the plating time. in all of them, the AChR was spread over the cell membrane. More than one AChR ionic channel conductance was observed in P and T cultures, and the prevalent value of gamma in either culture ranged from 30 pS to 35 pS. in P fibers from 4-day-old rats cultured for 7 days (P 4/7), the distribution of channel open times fitted a double exponential, while in T 4/7 they were fitted with a single exponential. in cultures from P and T muscles obtained from older rats (6 days old) and in those cells remaining in culture for a prolonged time (15 days), the channel open times also fitted a double exponential. Because P and T cultures lack trophic neuronal influences, the difference observed between the tau of P 4/7 and T 4/7 was thought to be the hormone requirement of P muscles to grow and differentiate. Likewise, the difference observed between T 4/7 and T 4/15 may indicate the need for neurotrophic influences to maintain higher T values in older cultures. Since this requirement is not found in cultured fibers, tau would tend to assume slower values approaching those of P without hormone activation.