The Electrogenic NA+,K+-Pump in Smooth Muscle: Physiologic and Pharmacologic Significance

Fleming, William W.

doi:10.1146/annurev.pa.20.040180.001021

Cited by 180 publications

(80 citation statements)

References 33 publications

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“…A close association between the degree of depolarization of smooth muscle cells and their sensitivity to various agonists has been suggested by Fleming (1980). Mulvany et al (1982) also demonstrated that depolarization increased the sensitivity of rat mesenteric arterioles to NA.…”

Section: Discussionmentioning

confidence: 67%

Potentiation by neuropeptide Y of vasoconstriction in rat resistance arteries

Andriantsitohaina

Stoclet

1988

British J Pharmacology

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1 The effects of neuropeptide Y (NPY) on resistance arteries were investigated on 3rd generation mesenteric arterioles of the rat.2 Contractions were elicited by noradrenaline (NA), 5-hydroxytryptamine (5-1HT), prostaglandin F2, (PGF2j), depolarization (KCI substituted for NaCl) and by the calcium agonist Bay K 8644, in the absence and in the presence of NPY (100nM), a concentration which by itself did not induce vasoconstriction. 3 NPY produced a leftward shift of the concentration-response curves to the agonists and to KCl, without any alteration of maximal contractions. 4 NPY also potentiated contractions elicited by addition of CaCl2 to KCl-depolarized vessels, but its effect on calcium-induced contractions decreased with increasing KCl concentrations (from 20 to 100mM). 5 Calcium-induced contractions were inhibited by the calcium channel blocker nitrendipine, both in the presence and absence of NPY (100nM). NPY increased slightly (but significantly) the sensitivity to nitrendipine (the apparent KB increased from 2.9 x 10-1°M to 1.6 x 10-10 M). 6 The KCl concentration necessary for the maximal effect of Bay K 8644 was decreased in the presence of NPY, and the sensitivity to the calcium channel agonist was increased. 7 Elevating the KCI concentration in the bath from 5 to 20mM (which gives the same displacement to the left of the KCI concentration-effect curve seen in the presence of NPY) induced a parallel leftward shift of NA and 5-HT concentration-response curves. This shift was identical to the one induced by NPY on 5-HT-evoked contractions, but it was significantly smaller (P < 0.001) than the shift of the NA concentration-response curve observed in the presence of NPY. In the latter case, NPY enhanced more markedly the contractions induced by low NA concentrations (between 10-' and 3 x 10-8M) than those induced by high concentrations (up to 3 x 10-7M), thus giving a shallow concentration-response curve. 8 The results strongly suggest that NPY partially depolarizes the arterioles and induces an increase in calcium entry through voltage-dependent channels, thus enhancing contractions elicited by agonists or by KCI-depolarization. In addition, they support the view that another mechanism also plays a part in the potentiation by NPY of the effects of low concentrations of NA.

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Section: Discussionmentioning

confidence: 67%

Potentiation by neuropeptide Y of vasoconstriction in rat resistance arteries

Andriantsitohaina

Stoclet

1988

British J Pharmacology

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“…In normal aortae, ouabain-induced vascular contraction is caused by membrane depolarization caused by Na ϩ /K ϩ ATPase inhibition. 1,5 Ouabain induces vascular contraction only if Na ϩ /K ϩ ATPase is active under baseline conditions. 1,5 Because baseline Na ϩ /K ϩ ATPase activity is decreased in cirrhotic aortae (see above), this decrease may explain the cirrhosis-induced hyporeactivity to ouabain-elicited vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

Effects of protein kinase C modulators on Na+/K+ adenosine triphosphatase activity and phosphorylation in aortae from rats with cirrhosis

Lahaye

Tazi

Rona³

et al. 1998

Hepatology

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Protein kinase C (PKC) modulates the activity and phosphorylation of the catalytic ␣-subunit of sodiumpotassium-adenosine triphosphatase (Na ؉ /K ؉ ATPase) in normal arteries. Because PKC is altered in cirrhotic aortae, Na ؉ /K ؉ ATPase may also be altered in these arteries. The aim of the present study was to investigate ␣-subunit activity and phosphorylation in aortae from normal and cirrhotic rats, under baseline conditions and during exposure to PKC modulators. ␣-Subunit activity was assessed by measuring the amount of 32 P released by hydrolysis of [␥-32 P]ATP in freshly isolated cell membranes (in the absence of PKC modulators only) and membrane depolarization caused by ouabain-induced ␣-subunit inhibition in isolated aortae (in the absence and presence of PKC modulators). ␣-Subunit phosphorylation was assessed by incorporation of 32 P into ␣-subunits. Staurosporine, a PKC inhibitor, and phorbol 12,13-dibutyrate (PDBU), a PKC activator, were used. In addition, ␣-subunit expression was studied by Western blot analysis. In the absence of PKC modulators, the amount of 32 P released by hydrolysis of [␥-32 P]ATP and ouabain-induced membrane depolarization were significantly lower in cirrhotic than in normal aortae. Staurosporine suppressed ouabain-induced membrane depolarization in cirrhotic and normal arteries. Ouabaininduced membrane depolarization was similar in cirrhotic aortae exposed to PDBU and in normal arteries studied under baseline conditions. ␣-Subunit phosphorylation was significantly lower in cirrhotic than in normal aortae, in aortae under baseline conditions, and in arteries exposed to staurosporine. Phosphorylation of the ␣-subunit was similar in cirrhotic aortae exposed to PDBU and in normal arteries under baseline conditions. Western blot analysis showed that the amount of ␣-subunit did not significantly differ between cirrhotic and normal aortae. In conclusion, a decrease in baseline Na ؉ /K ؉ ATPase ␣-subunit activity occurs in aortae from cirrhotic rats as a result of reduced basal PKC activity. This PKC-dependent decreased ␣-subunit activity may be caused by a reduction in PKC-induced ␣-subunit phosphorylation. (HEPATOLOGY 1998;28:663-669.)

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“…Finally, pretreatment of tissues with Rp-cAMPS, a cAMP-dependent protein kinase inhibitor, or KT5823, a cGMPdependent protein kinase inhibitor [13], had no effect on the TJ-17-and TJ-23-induced inhibition, indicating that the involvement of these cyclic nucleotides is not likely. There is ample evidence that Ca 2+ -activated K + channel and Na + -K + ATPase, an enzyme responsible for the electrochemical gradient of Na + and K + across the cell membrane, are present on airway smooth muscle cells and play an important role in the regulation of the contractility [7,8]. The opening of Ca 2+ -activated K + channels and stimulation of Na + -K + ATPase activity may reduce smooth muscle contraction by increasing the Na + /Ca 2+ exchange and inhibiting the Ca 2+ influx through the membrane potential-dependent Ca 2+ channel [22].…”

Section: Discussionmentioning

confidence: 99%

“…Stimulation of enzymatic activity of Na + -K + ATPase may lead to generation of the sodium gradient necessary to exclude calcium (Ca 2+ ) via the Na + /Ca + exchange or hyperpolarization of the membrane, which in turn reduces Ca 2+ influx through membrane potential-dependent Ca 2+ channels [8]. It has recently been shown that TJ-17 and TJ-23 protect brain cells against apoptosis by elevating Na + -K + ATPase activity of microvascular beds [9].…”

mentioning

confidence: 99%

Inhibition of airway smooth muscle tone by Chinese herbal medicines

Tagaya¹,

Tamaoki²,

Kawatani³

et al. 2000

Eur Respir J

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The aim of the present study was to elucidate whether Chinese traditional herbal drugs, Gorei-San (TJ-17) and Toki-Shakuyaku-San (TJ-23), affect airway smooth muscle tone and, if so, to determine what the mechanism of action is.Rabbit tracheal segments were isolated and the contractile responses to electrical field stimulation and acetylcholine were measured before and after the application of TJ-17 or TJ-23 under isometric conditions in vitro. Ouabain-sensitive rubidium-86 ( 86 Rb) uptake by tissues in response to each drug was also measured.Each herbal medicine attenuated the contractile responses to electrical field stimulation and acetylcholine in a concentration-dependent manner, the maximal inhibition of acetylcholine-induced contraction being 37.5 4.9% for TJ-17 and 42.4 5.3% for TJ-23 (p<0.05 for each). These effects were not altered by mechanical removal of the epithelium, indomethacin, the nitric oxide synthase inhibitor N G -nitro-L-arginine methyl ester, the cyclic adenosine monophosphate (cAMP)-dependent protein kinase inhibitor adenosine 3'5'-cyclic monophosphorothiioate (Rp-cAMPS), the cyclic guanosine monophosphate (cGMP)-dependent protein kinase inhibitor KT5823, or the calcium (Ca 2+ )-activated potassium (K + ) channel inhibitor charybdotoxin, but were greatly inhibited in the presence of the sodium (Na + )-K + adenosine triphosphatase (ATPase) inhibitor ouabain. Incubation of tissues with TJ-17 and TJ-23 dose dependently increased ouabain-sensitive 86 Rb uptake.The results of the study suggest that both Gorei-San and Toki-Shakuyaku-San reduce airway smooth muscle tone via a postjunctional mechanism probably through stimulation of the sodium pump and the subsequent hyperpolarization/repolarization of the cell membrane. These effects may contribute to the antiasthmatic properties of these herbal medicines.

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The Electrogenic NA+,K+-Pump in Smooth Muscle: Physiologic and Pharmacologic Significance

Cited by 180 publications

References 33 publications

Potentiation by neuropeptide Y of vasoconstriction in rat resistance arteries

Potentiation by neuropeptide Y of vasoconstriction in rat resistance arteries

Effects of protein kinase C modulators on Na+/K+ adenosine triphosphatase activity and phosphorylation in aortae from rats with cirrhosis

Inhibition of airway smooth muscle tone by Chinese herbal medicines

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