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1.
Physiol Rep ; 12(6): e15992, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38538032

RESUMO

Aorta, the largest vessel in the body, is generally considered anatomically homogeneous, yet spatial functional differences exist. In our study, we conducted a comprehensive analysis by reexamining public RNA-SEQ data, comparing expression patterns between thoracic and abdominal aorta. Additionally, we measured acetylcholine-induced relaxations of the different regions of thoracic aorta in Wistar Rats. Our results revealed a distinct percentage difference in acetylcholine-induced relaxation in the proximal and distal segments of the thoracic aorta (p = 1.14e-4). To explain this variation, we performed differential expression analysis of previously published RNA-sequencing data between thoracic and abdominal aorta, which showed 497 differentially expressed genes between these locations. From results of RNA-Seq analysis, we draw a hypothesis that differential expressions of the potassium inward rectifying channels (KIR) and voltage gated calcium channels (VGCC) presumably located on SMC, with higher expression in the distal thoracic segments in comparison with the proximal thoracic segments of aorta, can explain differences in acetylcholine-induced relaxation. Notably, specific blockade of KIR eliminated differences between the proximal and distal regions of thoracic aorta, underscoring their significance in understanding the spatial nuances in aortic behavior, also blockade of VGCC, shows a higher effect on basal tone, in distal region of thoracic aorta in comparison with proximal.


Assuntos
Acetilcolina , Aorta Torácica , Ratos , Masculino , Animais , Acetilcolina/farmacologia , Ratos Wistar , Endotélio Vascular , Vasodilatação , Aorta Abdominal , Canais de Potássio , Canais de Cálcio
2.
Fiziol Zh (1994) ; 62(1): 25-33, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29537197

RESUMO

The revue deals with the role of each component of adenylate cyclase regulatory system in the rat myometrial contractile activity modulation by the peptidoglycane of Staphylococcus aureus. Noradrenalin and salbutamol were used to investigate peptidoglycane impact on the myometrial ß-adrenergic receptors. It was shown that inhibited by these substances myometrial contractility increased to the initial level after peptidoglycane application. The same effect we observed under the cAMP level elevation by forscolin. Peptidoglycan' s ability to strengthen contractions was inhibited by the 8-brom-cAMP and papaverine application. Stimulation of Gs-protein by the cholera toxin didn't influence on the peptidoglycane effect while the blocking of Gi/o-protein by the pertussis toxin caused stopping it's manifestation. We concluded that the modulating effect of peptidoglycane implemented via Gi/o-protein activation, which causes adenilatcyclase desensitization.


Assuntos
Adenilil Ciclases/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Miométrio/efeitos dos fármacos , Peptidoglicano/farmacologia , Contração Uterina/efeitos dos fármacos , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Adenilil Ciclases/genética , Agonistas alfa-Adrenérgicos/farmacologia , Agonistas de Receptores Adrenérgicos beta 2 , Albuterol/farmacologia , Animais , Parede Celular/química , Toxina da Cólera/farmacologia , Colforsina/farmacologia , Feminino , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/antagonistas & inibidores , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/antagonistas & inibidores , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica/fisiologia , Miométrio/fisiologia , Norepinefrina/farmacologia , Papaverina/farmacologia , Toxina Pertussis/farmacologia , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Staphylococcus aureus/química , Técnicas de Cultura de Tecidos , Contração Uterina/fisiologia
4.
Br J Pharmacol ; 129(4): 695-702, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10683194

RESUMO

The effects of SK&F 96365 on cationic current evoked either by activating muscarinic receptors with carbachol or by intracellularly applied GTPgammaS (in the absence of carbachol) were studied using patch-clamp recording techniques in single guinea-pig ileal smooth muscle cells. SK&F 96365 reversibly inhibited the muscarinic receptor cationic current in a concentration-, time- and voltage-dependent manner producing concomitant alteration of the steady-state I-V relationship shape which could be explained by assuming that increasing membrane positivity increased the affinity of the blocker. The inhibition was similar for both carbachol- and GTPgammaS-evoked currents suggesting that the cationic channel rather than the muscarinic receptor was the primary site of the SK&F 96365 action. Increased membrane positivity induced additional rapid inhibition of the cationic current by SK&F 96365 which was more slowly relieved during membrane repolarization. Both the inhibition and disinhibition time course could be well fitted by a single exponential function with the time constants decreasing with increasing positivity for the inhibition (e-fold per about 12 mV) and approximately linearly decreasing with increasing negativity for the disinhibition. At a constant SK&F 96365 concentration, the degree of cationic current inhibition was a sigmoidal function of the membrane potential with a potential of half-maximal increase positive to about +30 mV and a slope factor of about -13 mV. Increasing the duration of voltage steps at -80 or at 80 mV, increased the percentage inhibition; the degree of inhibition was almost identical at both potentials providing evidence that the same cationic channel was responsible for the cationic current both at negative and at positive potentials. It is concluded that the distinctive and unique mode of SK&F 96365 action on the muscarinic receptor cationic channel is a valuable tool in future molecular biology studies of this channel.


Assuntos
Imidazóis/farmacologia , Canais Iônicos/antagonistas & inibidores , Antagonistas Muscarínicos/farmacologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Receptores Muscarínicos/fisiologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Carbacol/farmacologia , Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia , Cobaias , Íleo/citologia , Íleo/efeitos dos fármacos , Íleo/fisiologia , Canais Iônicos/fisiologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Liso/citologia , Receptores Muscarínicos/metabolismo
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