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

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.


Acetylcholine , Aorta, Thoracic , Rats , Male , Animals , Acetylcholine/pharmacology , Rats, Wistar , Endothelium, Vascular , Vasodilation , Aorta, Abdominal , Potassium Channels , Calcium Channels
2.
Fiziol Zh (1994) ; 62(1): 25-33, 2016.
Article En | MEDLINE | ID: mdl-29537197

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.


Adenylyl Cyclases/metabolism , Gene Expression Regulation/drug effects , Myometrium/drug effects , Peptidoglycan/pharmacology , Uterine Contraction/drug effects , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Adenylyl Cyclases/genetics , Adrenergic alpha-Agonists/pharmacology , Adrenergic beta-2 Receptor Agonists , Albuterol/pharmacology , Animals , Cell Wall/chemistry , Cholera Toxin/pharmacology , Colforsin/pharmacology , Female , GTP-Binding Protein alpha Subunits, Gi-Go/antagonists & inhibitors , GTP-Binding Protein alpha Subunits, Gi-Go/genetics , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , GTP-Binding Protein alpha Subunits, Gs/antagonists & inhibitors , GTP-Binding Protein alpha Subunits, Gs/genetics , GTP-Binding Protein alpha Subunits, Gs/metabolism , Gene Expression Regulation/physiology , Myometrium/physiology , Norepinephrine/pharmacology , Papaverine/pharmacology , Pertussis Toxin/pharmacology , Rats , Rats, Wistar , Receptors, Adrenergic, beta-2/genetics , Receptors, Adrenergic, beta-2/metabolism , Staphylococcus aureus/chemistry , Tissue Culture Techniques , Uterine Contraction/physiology
4.
Br J Pharmacol ; 129(4): 695-702, 2000 Feb.
Article En | MEDLINE | ID: mdl-10683194

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.


Imidazoles/pharmacology , Ion Channels/antagonists & inhibitors , Muscarinic Antagonists/pharmacology , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Receptors, Muscarinic/physiology , Animals , Calcium Channel Blockers/pharmacology , Carbachol/pharmacology , Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology , Guinea Pigs , Ileum/cytology , Ileum/drug effects , Ileum/physiology , Ion Channels/physiology , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Smooth/cytology , Receptors, Muscarinic/metabolism
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