Comparative Studies on the Relaxing Action of Several Adenosine 5'-Triphosphate-Sensitive K+ Channel Openers in Pig Urethra.

Teramoto, Noriyoshi; Ito, Yushi

doi:10.1540/jsmr.35.11

Cited by 7 publications

(5 citation statements)

References 13 publications

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“…Thus, although pinacidil activates two different types of K channel in some vascular smooth muscle cells (rat portal vein (Zhang & Bolton 1996); human coronary artery (Bychkov et al 1997)), it is likely that in pig urethra, K ATP channel is the only target K channel for pinacidil at the resting membrane potential. Our results are also supported by our previous observations that the pinacidil-induced relaxation in pig urethra was selectively suppressed by additional application of glibenclamide in tension recordings (Teramoto & Ito 1999).…”

Section: Discussionsupporting

confidence: 91%

“…Despite the common vasodilator action of pinacidil, it still remains uncertain whether or not the different target K channels arise from different experimental conditions or are species-dependent even in vascular smooth muscle. The potent relaxant effects of pinacidil on nonvascular smooth muscles in intact tissues have also been widely investigated (guinea-pig ileum, Sun & Benishin (1994); rat intestine, Davies et al (1996); guineapig detrusor, Gopalakrishnan et al (1999); pig urethra, Teramoto & Ito (1999)) and a possible clinical role for pinacidil in several diseases has been suggested (Andersson 1992). Therefore, we believe that direct investigations of the effects of pinacidil are essential in non-vascular smooth muscle as well as in vascular smooth muscle.…”

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confidence: 96%

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Possible Underestimation of the Channel Conductance Underlying Pinacidil-induced K+ Currents Using Noise Analysis in Pig Urethral Myocytes

Teramoto

Brading²,

Ito

2000

Journal of Pharmacy and Pharmacology

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Electrophysiological and pharmacological properties of the pinacidil-induced K+ currents in isolated cells from pig urethra were investigated using patch-clamp techniques. Pinacidil (100 microM) induced an outward current at -50 mV which gradually decreased. Under current-clamp conditions, 100 microM pinacidil induced a hyperpolarization that was sustained. This suggests that activation of only a few channels can hyperpolarize the membrane. At a holding potential of -50 mV, glibenclamide inhibited the pinacidil-induced current with a single exponential time course. Unitary current recordings in symmetrical 140 mM K+ conditions demonstrated that pinacidil activates a 43-pS, glibenclamide-sensitive K+ channel (i.e. K(ATP) channel). Analysis of the basal noise of the pinacidil-induced macroscopic currents from -90 mV to -30 mV yielded estimates of channel conductance (6 pS) which were much smaller, and probably an underestimate. These results indicate that pinacidil induces a glibenclamide-sensitive K+ current through only one type of K+ channel (K(ATP) channel) in pig urethra.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 96%

Possible Underestimation of the Channel Conductance Underlying Pinacidil-induced K+ Currents Using Noise Analysis in Pig Urethral Myocytes

Teramoto

Brading²,

Ito

2000

Journal of Pharmacy and Pharmacology

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“…bars are less than the size of the symbol. The urethral relaxing curve with the broken line is for the effects of levcromakalim ( K =0.3 μ M , n H =2.1, n =18), and is taken from Teramoto & Ito (1999).…”

Section: Resultsmentioning

confidence: 99%

“…For isometric tension recording, fine strips were prepared as described previously (Teramoto & Ito, 1999). An initial tension equivalent to 1 g weight was applied to each strip, which was then allowed to equilibrate for approximately 1 – 1.5 h until the basal urethral tone became stable (37°C).…”

Section: Methodsmentioning

confidence: 99%

The involvement of L‐type Ca²⁺ channels in the relaxant effects of the ATP‐sensitive K⁺ channel opener ZD6169 on pig urethral smooth muscle

Teramoto

Yunoki

Ikawa

et al. 2001

British J Pharmacology

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1 The e ects of ZD6169, a novel ATP-sensitive K + channel (K ATP channel) opener, were investigated on membrane currents in isolated myocytes using patch-clamp techniques. Tension measurement was also performed to study the e ects of ZD6169 on the resting tone of pig urethral smooth muscle. 2 Levcromakalim was more potent than ZD6169 in lowering the resting urethral tone. Relaxation induced by low concentrations of ZD6169 (43 mM) was completely suppressed by additional application of glibenclamide (1 mM). In contrast, glibenclamide (1 ± 10 mM) only partially inhibited the relaxation induced by higher concentrations of ZD6169 (510 mM). 3 Bay K8644 (1 mM) reduced the maximum relaxation produced by ZD6169 (510 mM). 4 In whole-cell con®guration, ZD6169 suppressed the peak amplitude of voltage-dependent Ba 2+ currents in a concentration-and voltage-dependent manner, and at 100 mM, shifted the steady-state inactivation curve of the voltage-dependent Ba 2+ currents to the left at a holding potential of 790 mV. 5 In cell-attached con®guration, open probability of unitary voltage-dependent Ba 2+ channels (27 pS, 90 mM Ba 2+ ) was inhibited by 100 mM ZD6169 and by 10 mM nifedipine. 6 Reverse transcriptase-polymerase chain reaction (RT ± PCR) analysis revealed the presence of the transcript of the a 1C subunit of L-type Ca 2+ channels in pig urethra. 7 These results demonstrate that ZD6169 causes urethral relaxation through two distinct mechanisms, activation of K ATP channels at lower concentrations and inhibition of voltagedependent Ca 2+ channels at higher concentrations (about 10 mM).

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“…K ATP channels have also been identified in pig proximal urethra, and have been quite extensively characterised in this tissue [177]. They have a unitary conductance of 43 pS and are activated by metabolic inhibition and intracellular nucleotide diphosphates as well as by K ATP channel openers [177][178][179], which also relaxed urethral strips with the order of potency levcromakalim> pinacidil>diazoxide>minoxidil [180]. The channels were also active in the absence of stimulation, and glibenclamide caused a significant depolarization of smooth muscle in urethral strips, consistent with a role for K ATP channels in maintenance of the membrane potential in urethra as well as bladder [181].…”

Section: Urinary Bladder and Urinary Tractmentioning

confidence: 99%

ATP-Sensitive Potassium Channels

Rodrigo

Standen²

2005

CPD

105

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ATP-sensitive potassium (K(ATP)) channels link membrane excitability to metabolism. They are regulated by intracellular nucleotides and by other factors including membrane phospholipids, protein kinases and phosphatases. K(ATP) channels comprise octamers of four Kir6 pore-forming subunits associated with four sulphonylurea receptor subunits. The exact subunit composition differs between the tissues in which the channels are expressed, which include pancreas, cardiac, smooth and skeletal muscle and brain. K(ATP) channels are targets for antidiabetic sulphonylurea blockers, and for channel opening drugs that are used as antianginals and antihypertensives. This review focuses on non-pancreatic K(ATP) channels. In vascular smooth muscle, K(ATP) channels are extensively regulated by signalling pathways and cause vasodilation, contributing both to resting blood flow and vasodilator-induced increases in flow. Similarly, K(ATP) channel activation relaxes smooth muscle of the bladder, gastrointestinal tract and airways. In cardiac muscle, sarcolemmal K(ATP) channels open to protect cells under stress conditions such as ischaemia or exercise, and appear central to the protection induced by ischaemic preconditioning (IPC). Mitochondrial K(ATP) channels are also strongly implicated in IPC, but clarification of their exact role awaits information on their molecular structure. Skeletal muscle K(ATP) channels play roles in fatigue and recovery, K+ efflux, and glucose uptake, while neuronal channels may provide ischaemic protection and underlie the glucose-responsiveness of hypothalamic neurones. Current therapeutic considerations include the use of K(ATP) openers to protect cardiac muscle, attempts to develop openers selective for airway or bladder, and the question of whether block of extra-pancreatic K(ATP) channels may cause adverse cardiovascular side-effects of sulphonylureas.

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Comparative Studies on the Relaxing Action of Several Adenosine 5'-Triphosphate-Sensitive K+ Channel Openers in Pig Urethra.

Cited by 7 publications

References 13 publications

Possible Underestimation of the Channel Conductance Underlying Pinacidil-induced K+ Currents Using Noise Analysis in Pig Urethral Myocytes

Possible Underestimation of the Channel Conductance Underlying Pinacidil-induced K+ Currents Using Noise Analysis in Pig Urethral Myocytes

The involvement of L‐type Ca²⁺ channels in the relaxant effects of the ATP‐sensitive K⁺ channel opener ZD6169 on pig urethral smooth muscle

ATP-Sensitive Potassium Channels

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Comparative Studies on the Relaxing Action of Several Adenosine 5'-Triphosphate-Sensitive K+ Channel Openers in Pig Urethra.

Cited by 7 publications

References 13 publications

Possible Underestimation of the Channel Conductance Underlying Pinacidil-induced K+ Currents Using Noise Analysis in Pig Urethral Myocytes

Possible Underestimation of the Channel Conductance Underlying Pinacidil-induced K+ Currents Using Noise Analysis in Pig Urethral Myocytes

The involvement of L‐type Ca2+ channels in the relaxant effects of the ATP‐sensitive K+ channel opener ZD6169 on pig urethral smooth muscle

ATP-Sensitive Potassium Channels

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The involvement of L‐type Ca²⁺ channels in the relaxant effects of the ATP‐sensitive K⁺ channel opener ZD6169 on pig urethral smooth muscle