Inhibition of α-adrenergic responses in the rat liver by lipophilic K+ channel blockers or depolarizing Cl− gradients. Evidence for a potential-sensitive step in the signal transduction path

1993 ◽  
Vol 71 (5-6) ◽  
pp. 229-235 ◽  
Author(s):  
Ceredwyn E. Hill ◽  
David O. Ajikobi
Keyword(s):  
Signal Transduction ◽  
Rat Liver ◽  
Potential Role ◽  
Portal Pressure ◽  
K Channel ◽  
Second Phase ◽  
Channel Blockers ◽  
Adrenergic Stimulation ◽  
Glucose Release

To study the role of K+ channels and membrane potential in α-adrenergic responses of the rat liver, lipophilic K+ channel blockers quinidine and 4-aminopyridine were used or external Cl− was replaced with gluconate, an impermeant ion. Glucose release, O2 uptake, portal pressure, and K+ flux were measured in the isolated perfused liver. The α-agonist phenylephrine caused biphasic changes in each parameter, a fast transient followed by sustained elevated responses. Infusion of 5 mM 4-aminopyridine, 0.1 mM quinidine, or gluconate prior to phenylephrine inhibited each parameter, with the greatest inhibition occurring during the second phase. A similar pattern was seen with 2 mM EGTA. This contrasts with the full inhibition of all responses following exposure to the α-antagonist phentolamine. Infusion of each inhibitor at the peak of the sustained phase inhibited all responses. Phenylephrine-stimulated release of K+ was augmented in the presence of EGTA and was inhibited by 4-aminopyridine or quinidine. In contrast, β-adrenergic stimulation of glucose release and K+ flux were not affected by the K+ channel blockers. Phenylephrine-stimulated glucose release from hepatocyte suspensions decreased by about 50% in the presence of 4-aminopyridine, EGTA, or gluconate. The results are discussed in terms of a potential role for K+ channels in α-adrenergic signal transduction in the liver.Key words: perfusion, hepatocyte, glycogenosis, haemodynamics, pinacidil.

Cholestatic effects of the K+ channel blockers Ba2+ and TEA occur through different pathways in the rat liver

1999 ◽  
Vol 276 (1) ◽  
pp. G43-G48 ◽  
Author(s):  
Ceredwyn Elizabeth Hill ◽  
Jody Elisabeth Jacques
Keyword(s):  
Rat Liver ◽  
Driving Force ◽  
Bile Flow ◽  
Portal Pressure ◽  
Boltzmann Distribution ◽  
Equilibrium Potential ◽  
K Channel ◽  
Channel Blockers ◽  
Channel Activity ◽  
Bile Formation

The role of K+ channels in bile acid-independent bile flow (BAIF) was studied in the isolated and bile duct-cannulated perfused rat liver by changing the driving force on K+and by using a variety of K+channel blockers. Bile flow rate, effluent perfusate K+ content, and portal pressure were measured. Increase in perfusate K+ from 5.9 to 80 mM caused inhibition of bile flow that could be fitted to a Boltzmann distribution, indicating partial dependence of bile formation on the K+ equilibrium potential and hence K+ channel activity. To investigate this further, the effects of compounds established as K+ channel blockers in liver or other tissues were surveyed. Ba2+ (1–5 mM) inhibited mean bile flow by 20%. Tetraethylammonium (TEA) inhibition of basal bile flow was biphasic with saturable (IC50 ∼0.7 mM) and linear components. In contrast, infusion of the K+ channel blockers 4-aminopyridine (5 mM), cesium (2.5 mM), quinidine (0.1 mM), iberiotoxin (90 nM), or paxilline (100 nM) did not affect bile flow. As expected for a K+ channel blocker, Ba2+ caused a net K+ uptake. Conversely, TEA did not affect basal K+ fluxes, although TEA-induced cholestasis was accompanied by a 26% decrease in biliary glutathione excretion. These results suggest that the partial cholestasis induced by the K+channel blockers Ba2+ and TEA occurs by significantly different mechanisms. Whereas the Ba2+ response implicates K+ channel activity as a significant driving force in BAIF, TEA-sensitive K+ channels are not present or are not involved in bile formation.

scholarly journals Potential role of luminal potassium in tubuloglomerular feedback.

1997 ◽  
Vol 8 (12) ◽  
pp. 1831-1837 ◽  
Author(s):  
V Vallon ◽  
H Osswald ◽  
R C Blantz ◽  
S Thomson
Keyword(s):  
Potential Role ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
K Channel ◽  
Thick Ascending Limb ◽  
Retrograde Perfusion ◽  
Luminal Membrane ◽  
K Concentration ◽  
Tubular Flow

Transport through the Na+-2Cl(-)-K+ cotransporter in the luminal membrane of macula densa cells is considered critical for tubuloglomerular feedback (TGF). Although various studies could support the importance of luminal Na+ and Cl-, the role of luminal K+ in TGF has not been thoroughly addressed. The study presented here examines this issue in nephrons with superficial glomeruli of anesthetized male Munich-Wistar-Frömter rats. Ambient Na+ concentration in early distal tubular fluid was approximately 22 mM, suggesting collection sites relatively close to the macula densa segment. First, it was found that ambient early distal tubular K+ concentration is approximately 1.3 mM, i.e., close to the K+ affinity of the Na+-2Cl(-)-K+ cotransporter in the thick ascending limb. Second, it was observed that a change in late proximal tubular flow rate, i.e., a maneuver that is known to induce a TGF response, significantly alters early distal tubular K+ concentration. Third, previous experiments failed to show an inhibition in TGF response during retrograde perfusion of the macula densa with K+-free solutions. Because of a potential K+ influx into the lumen between the perfusion site and the macula densa, however, the K+ channel blocker U37883A was added to the K+-free perfusate. TGF response was assessed as the fall in nephron filtration rate in response to retrograde perfusion of the macula densa segment from early distal tubular site. It was observed that luminal U37883A (100 microM) significantly attenuated TGF. Because adding 5 mM KCl to the perfusate restored TGF in the presence of U37883A and because the inhibitory action of U37883A on tubular K+ secretion was confirmed, the effect of U37883A on TGF was most likely caused by inhibition of K+ influx into the perfused segment, which decreased luminal K+ concentration at the macula densa. The present findings support a potential role for luminal K+ in TGF, which is in accordance with a transmission of the TGF signal across the macula densa via Na+-2Cl(-)-K+ cotransporter.

GCSF Partially Repairs Heart Damage Induced by Repetitive β-adrenergic Stimulation in Mice: Potential Role of the Mobilized Bone Marrow-derived Cells

2016 ◽  
Vol 12 (7) ◽  
pp. 689-700 ◽  
Author(s):  
B. Nieto-Lima ◽  
A. Cano-Marti ◽  
G. Zarco-Olve ◽  
F.A. Masso-Roja ◽  
A. Paez-Arena ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Potential Role ◽  
Adrenergic Stimulation ◽  
Heart Damage ◽  
Bone Marrow Derived Cells

scholarly journals The role of interleukin-6 in intracellular signal transduction after chronic β-adrenergic stimulation in mouse myocardium

2019 ◽  
Vol 15 (6) ◽  
pp. 1565-1575 ◽  
Author(s):  
Magdalena Dziemidowicz ◽  
Tomasz Bonda ◽  
Siergiej Litvinovich ◽  
Andrzej Taranta ◽  
Maria Winnicka ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Interleukin 6 ◽  
Adrenergic Stimulation ◽  
Intracellular Signal Transduction ◽  
Intracellular Signal

Inflammation response after the cessation of chronic arsenic exposure and post-treatment of natural astaxanthin in liver: potential role of cytokine-mediated cell–cell interactions

2020 ◽  
Vol 11 (10) ◽  
pp. 9252-9262 ◽  
Author(s):  
Zhigang Zhang ◽  
Changming Guo ◽  
Huijie Jiang ◽  
Bing Han ◽  
Xiaoqiao Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Rat Liver ◽  
Potential Role ◽  
Arsenic Exposure ◽  
Post Treatment ◽  
Cell Interactions ◽  
Schematic Diagram ◽  
Inflammation Response ◽  
Chronic Arsenic Exposure

Schematic diagram of the mechanism of post treatment with natural astaxanthin attenuating arsenic-induced inflammatory response in rat liver.

scholarly journals Cardiac preconditioning with 4-h, 17°C ischemia reduces [Ca2+]i load and damage in part via KATP channel opening

2002 ◽  
Vol 282 (6) ◽  
pp. H1961-H1969 ◽  
Author(s):  
Qun Chen ◽  
Amadou K. S. Camara ◽  
Jianzhong An ◽  
Matthias L. Riess ◽  
Enis Novalija ◽  
...  
Keyword(s):  
Infarct Size ◽  
Potential Role ◽  
K Channel ◽  
Moderate Hypothermia ◽  
Channel Opening ◽  
Cardioprotective Effects ◽  
Hypothermic Storage ◽  
Cardiac Preconditioning

Brief ischemia before normothermic ischemia protects hearts against reperfusion injury (ischemic preconditioning, IPC), but it is unclear whether it protects against long-term moderate hypothermic ischemia. We explored in isolated guinea pig hearts 1) the influence of two 2-min periods of normothermic ischemia before 4 h, 17°C hypothermic ischemia on cardiac cytosolic [Ca2+], mechanical and metabolic function, and infarct size, and 2) the potential role of KATP channels in eliciting cardioprotection. We found that IPC before 4 h moderate hypothermia improved myocardial perfusion, contractility, and relaxation during normothermic reperfusion. Protection was associated with markedly reduced diastolic [Ca2+] loading throughout both hypothermic storage and reperfusion. Global infarct size was markedly reduced from 36 ± 2 (SE)% to 15 ± 1% with IPC. Bracketing ischemic pulses with 200 μM 5-hydroxydecanoic acid or 10 μM glibenclamide increased infarct size to 28 ± 3% and 26 ± 4%, respectively. These results suggest that brief ischemia before long-term hypothermic storage adds to the cardioprotective effects of hypothermia and that this is associated with decreased cytosolic [Ca2+] loading and enhanced ATP-sensitive K channel opening.

scholarly journals The action of α-adrenergic agonists on plasma-membrane calcium fluxes in perfused rat liver

1984 ◽  
Vol 220 (1) ◽  
pp. 43-50 ◽  
Author(s):  
P H Reinhart ◽  
W M Taylor ◽  
F L Bygrave
Keyword(s):  
Plasma Membrane ◽  
Rat Liver ◽  
Potential Role ◽  
Dependent Manner ◽  
Perfused Rat Liver ◽  
Adrenergic Agonists ◽  
Mediated Effects ◽  
Alpha Agonist ◽  
Alpha Adrenergic Agonist

The effect of alpha-adrenergic agonists on Ca2+ fluxes was examined in the perfused rat liver by using a combination of Ca2+-electrode and 45Ca2+-uptake techniques. We showed that net Ca2+ fluxes can be described by the activities of separate Ca2+-uptake and Ca2+-efflux components, and that alpha-adrenergic agonists modulate the activity of both components in a time-dependent manner. Under resting conditions, Ca2+-uptake and -efflux activities are balanced, resulting in Ca2+ cycling across the plasma membrane. The alpha-adrenergic agonists vasopressin and angiotensin, but not glucagon, stimulate the rate of both Ca2+ efflux and Ca2+ uptake. During the first 2-3 min of alpha-agonist administration the effect on the efflux component is the greater, the net effect being efflux of Ca2+ from the cell. After 3-4 min of phenylephrine treatment, net Ca2+ movements are essentially complete, however, the rate of Ca2+ cycling is significantly increased. After removal of the alpha-agonist a large stimulation of the rate of Ca2+ uptake leads to the net accumulation of Ca2+ by the cell. The potential role of these Ca2+ flux changes in the expression of alpha-adrenergic-agonist-mediated effects is discussed.

Determinants of renal microvascular response to ACh: afferent and efferent arteriolar actions of EDHF

2002 ◽  
Vol 282 (1) ◽  
pp. F124-F132 ◽  
Author(s):  
Xuemei Wang ◽  
Rodger Loutzenhiser
Keyword(s):  
Rat Kidney ◽  
K Channel ◽  
Channel Blockers ◽  
Efferent Arteriole ◽  
Microvascular Response ◽  
Vascular Beds ◽  
Underlying Mechanisms ◽  
Oxide Synthase

The renal microvascular actions of ACh were investigated using the in vitro perfused hydronephrotic rat kidney. ACh reversed ANG II-induced vasoconstriction in the afferent and efferent arteriole by 106 ± 2 and 75 ± 5%, respectively. Inhibition of nitric oxide synthase [NOS; 100 μmol/l N G-nitro-l-arginine methyl ester (l-NAME)] and cyclooxygenase (COX; 10 μmol/l ibuprofen) prevented the sustained response of the afferent arteriole but did not reduce the magnitude of the initial dilation (97 ± 7%). However, NOS/COX inhibition abolished the response of the efferent arteriole. The underlying mechanisms mediating this endothelium-derived hyperpolarizing factor (EDHF)-like response were characterized using K channel blockers. Ba (100 μmol/l), tetraethylammonium (1 mmol/l), and ouabain (3 mmol/l) had no effect, arguing against a role of an inward rectifier K channel, large-conductance Ca-activated K channel, or Na,K-ATPase. Charybdotoxin (10 nmol/l) and apamin (1.0 μmol/l) attenuated the response when administered alone (63 ± 7% and 37 ± 5%, respectively) and abolished the response when coadministered (0.1 ± 1.0%). These findings indicate that, as in other vascular beds, the renal EDHF-like response to ACh involves K channels that are sensitive to a combination of apamin and charybdotoxin. Our finding that EDHF modulates preglomerular, but not postglomerular, tone is consistent with the evolving concept that vasomotor mechanisms in cortical efferent arterioles do not involve voltage-gated Ca entry.

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