RESUMO
Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, a guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-1-methylxanthine, which promotes cyclic guanosine monophosphate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle.
Assuntos
Guanilato Ciclase/fisiologia , Contração Muscular/fisiologia , Relaxamento Muscular/fisiologia , Traqueia/inervação , 1-Metil-3-Isobutilxantina/farmacologia , Animais , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Estimulação Elétrica , Cobaias , Masculino , Azul de Metileno/farmacologia , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Nitroprussiato/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Descanso/fisiologiaRESUMO
Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-lmethylxanthine, which promotes cyclic guanosine monophospate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle(AU)
Assuntos
21003 , Cobaias , Contração Muscular/fisiologia , Guanilato Ciclase/fisiologia , Traqueia , GMP Cíclico/metabolismo , Estimulação Elétrica , Músculo Liso/fisiologiaRESUMO
Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-lmethylxanthine, which promotes cyclic guanosine monophospate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle
Assuntos
Animais , Cobaias , Traqueia , GMP Cíclico , Guanilato Ciclase/fisiologia , Contração Muscular/fisiologia , Estimulação Elétrica , Músculo Liso/fisiologiaRESUMO
Attenuated mutants of Venezuelan equine encephalitis virus (VEE) were isolated by selection for rapid penetration of cultured cells (R. E. Johnston and J. F. Smith, 1988, Virology 162, 437-443). Sequence analysis of these mutants identified candidate attenuating mutations at four loci in the VEE E2 glycoprotein gene: a double mutation at E2 codons 3 and 4, and single substitutions at E2 76, 120, and 209. Each candidate mutation was reproduced in an isogenic recombinant VEE strain using site-directed mutagenesis of a full-length cDNA clone of VEE. Characterization of these molecularly cloned mutant viruses showed that mutation at each of the four loci in the E2 gene was sufficient to confer both the accelerated penetration and attenuation phenotypes. Inoculation of the molecularly cloned viruses into rodent models that differ in their response to VEE suggested that individual mutations affected different aspects of VEE pathogenesis. Full-length clones containing multiple mutations were produced by combining independently attenuating mutations. Molecularly cloned viruses carrying two or three mutations were more attenuated in sensitive animal models than viruses which contained any single mutation alone. However, these highly attenuated strains still retained the ability to induce an immune response sufficient to protect against a high dose challenge with virulent VEE. These results indicate that production of a molecularly cloned live virus vaccine for VEE is feasible.