β-Adrenoceptors and potassium channels

Ferro, Albert

doi:10.1007/s00210-006-0065-2

Cited by 23 publications

(14 citation statements)

References 29 publications

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“…In view of the published evidence that activation of K Ca channels plays an important role in the regulation of β-AR-mediated relaxation and EDHF-mediated relaxation [13,14,18], we examined the contribution of such channels to ISO-mediated relaxation, in the presence of NOS/COX inhibition (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

Impaired β-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity

Matsumoto

Szasz

Tostes

et al. 2012

Pharmacological Research

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β-Adrenoceptor (β-AR)-mediated relaxation plays an important role in the regulation of vascular tone. β-AR-mediated vascular relaxation is reduced in various disease states and aging. We hypothesized that β-AR-mediated vasodilatation is impaired in DOCA-salt hypertension due to alterations in the cAMP pathway. β-AR-mediated relaxation was determined in small mesenteric arteries from DOCA-salt hypertensive and control uninephrectomized (Uni) rats. To exclude nitric oxide (NO) and cyclooxygenase (COX) pathways, relaxation responses were determined in the presence of L-NNA and indomethacin, NO synthase inhibitor and COX inhibitors, respectively. Isoprenaline (ISO)-induced relaxation was reduced in arteries from DOCA-salt compared to Uni rats. Protein kinase A (PKA) inhibitors (H89 or Rp-cAMPS) or adenylyl cyclase inhibitor (SQ22536) did not abolish the difference in ISO-induced relaxation between the groups. Forskolin (adenylyl cyclase activator)-induced relaxation was similar between the groups. The inhibition of IKCa/SKCa channels (TRAM-34 plus UCL1684) or BKCa channels (iberiotoxin) reduced ISO-induced relaxation only in Uni rats and abolished the relaxation differences between the groups. The expression of SKCa channel was decreased in DOCA-salt arteries. The expression of BKCa channel α subunit was increased whereas the expression of BKCa channel β subunit was decreased in DOCA-salt arteries. The expression of receptor for activated C kinase 1 (RACK1), which is a binding protein for BKCa channel and negatively modulates its activity, was increased in DOCA-salt arteries. These results suggest that the impairment of β-AR-mediated relaxation in DOCA-salt mesenteric arteries may be attributable to altered IKCa/SKCa and/or BKCa channels activities rather than cAMP/PKA pathway. Impaired β-AR-stimulated BKCa channel activity may be due to the imbalance between its subunit expressions and RACK1 upregulation.

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Section: Resultsmentioning

confidence: 99%

Impaired β-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity

Matsumoto

Szasz

Tostes

et al. 2012

Pharmacological Research

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“…Although cAMP/PKA is the main signal transduction pathway that mediates ␤3-AR effects, both PKA-dependent and -independent mechanisms have been proposed to operate in UBSM (11,12,45,47,48). Most of the information for a PKA-independent mechanism, however, comes from indirect evidence on UBSM contractility (12,47,48).…”

Section: Discussionmentioning

confidence: 96%

“…It is generally accepted that activation of ␤-ARs by agonists stimulates adenylyl cyclase to increase cAMP, which in turn, activates protein kinase A (PKA) to mediate UBSM relaxation. Recent studies show that agonist-induced stimulation of ␤-ARs causes activation of different K ϩ channels leading to membrane hyperpolarization and relaxation in various smooth muscle tissues (11,45). In guinea pig UBSM, isoproterenol, a nonselective ␤-AR agonist, inhibits spontaneous action potentials and hyperpolarizes the membrane through PKA activation (35).…”

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confidence: 99%

Stimulation of β3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca²⁺-activated K⁺ channels

Hristov¹,

Cui²,

Brown³

et al. 2008

American Journal of Physiology-Cell Physiology

113

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We investigated the role of large-conductance Ca(2+)-activated K(+) (BK) channels in beta3-adrenoceptor (beta3-AR)-induced relaxation in rat urinary bladder smooth muscle (UBSM). BRL 37344, a specific beta3-AR agonist, inhibits spontaneous contractions of isolated UBSM strips. SR59230A, a specific beta3-AR antagonist, and H89, a PKA inhibitor, reduced the inhibitory effect of BRL 37344. Iberiotoxin, a specific BK channel inhibitor, shifts the BRL 37344 concentration response curves for contraction amplitude, net muscle force, and tone to the right. Freshly dispersed UBSM cells and the perforated mode of the patch-clamp technique were used to determine further the role of beta3-AR stimulation by BRL 37344 on BK channel activity. BRL 37344 increased spontaneous, transient, outward BK current (STOC) frequency by 46.0 +/- 20.1%. In whole cell mode at a holding potential of V(h) = 0 mV, the single BK channel amplitude was 5.17 +/- 0.28 pA, whereas in the presence of BRL 37344, it was 5.55 +/- 0.41 pA. The BK channel open probability was also unchanged. In the presence of ryanodine and nifedipine, the current-voltage relationship in response to depolarization steps in the presence and absence of BRL 37344 was identical. In current-clamp mode, BRL 37344 caused membrane potential hyperpolarization from -26.1 +/- 2.1 mV (control) to -29.0 +/- 2.2 mV. The BRL 37344-induced hyperpolarization was eliminated by application of iberiotoxin, tetraethylammonium or ryanodine. The data indicate that stimulation of beta3-AR relaxes rat UBSM by increasing the BK channel STOC frequency, which causes membrane hyperpolarization and thus relaxation.

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“…In any cases, isoprenaline-induced relaxation Correspondence to: Yoshio Tanaka, Ph.D., Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Miyama 2-2-1, Funabashi-City, Chiba 274-8510, Japan Phone: +81-47-472-1435+81-47-472- Fax: +81-47-472-1448 of this vascular muscle should involve cAMP-dependent mechanisms since any of these β-AR subtypes are coupled to adenylyl cyclase via Gs protein (Tanaka et al, 2005). On the other hand, β-AR-mediated smooth muscle relaxations are not exclusively triggered through cAMPdependent mechanisms but also involve cAMP-independent mechanisms (Ferro, 2006;Horinouchi and Koike, 2002;Koike et al, 2004;Tanaka et al, 2003;Tanaka et al, 2005). However, little information is available so far on the possible contribution of cAMP-independent mechanisms to β-AR-mediated relaxation of vascular smooth muscle.…”

Section: Introductionmentioning

confidence: 99%

Studies on the mechanisms underlying .BETA.-adrenoceptor-mediated relaxation of rat abdominal aorta

Matsushita

Tanaka

Koike

2006

J. Smooth Muscle Res.

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Mechanisms underlying β-adrenoceptor (β-AR)-mediated vascular relaxation were studied in the isolated rat abdominal aorta. In the endothelium-denuded helical preparations, a non-selective β-AR agonist isoprenaline elicited a concentrationdependent relaxation. In the absence of β-AR antagonists, isoprenaline-induced relaxation was not practically affected by an adenylyl cyclase inhibitor SQ 22,536 (300 µM), but was strongly diminished by high-KCl (80 mM). Isoprenaline-induced relaxation in the presence of SQ 22,536 was significantly diminished by iberiotoxin (IbTx, 0.1 µM), but was not affected by 4-aminopyridine (4-AP, 3 mM). Isoprenaline-induced relaxation was not also affected by SQ 22,536 (300 µM) even in the presence of CGP20712A (a β1-selective antagonist) and ICI-118,551 (a β2-selective antagonist) (0.1 µM for each), but was strongly diminished by high-KCl. By contrast, SQ 22,536-resistant, isoprenalineinduced relaxation in the presence of CGP20712A plus ICI-118,551 was not affected by IbTx (0.1 µM), but was inhibited significantly by 4-AP (3 mM). These results suggest that in rat abdominal aortic smooth muscle: 1) both β1-/β2-AR-and β3-AR-mediated relaxations substantially involve cAMP-independent mechanisms; 2) β1-/β2-AR-mediated, cAMP-independent relaxant mechanisms are partly attributed to the large-conductance, Ca 2+ -sensitive K + (MaxiK, BK) channel whereas β3-AR-mediated relaxant mechanisms are attributed to Kv channel.

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β-Adrenoceptors and potassium channels

Cited by 23 publications

References 29 publications

Impaired β-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity

Impaired β-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity

Stimulation of β3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca²⁺-activated K⁺ channels

Studies on the mechanisms underlying .BETA.-adrenoceptor-mediated relaxation of rat abdominal aorta

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β-Adrenoceptors and potassium channels

Cited by 23 publications

References 29 publications

Impaired β-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity

Impaired β-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity

Stimulation of β3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca2+-activated K+ channels

Studies on the mechanisms underlying .BETA.-adrenoceptor-mediated relaxation of rat abdominal aorta

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Stimulation of β3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large-conductance Ca²⁺-activated K⁺ channels