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Article ; Online: Rab8a is involved in membrane trafficking of Kir6.2 in the MIN6 insulinoma cell line.

Uchida, Keiichiro / Nomura, Masatoshi / Yamamoto, Tadashi / Ogawa, Yoshihiro / Teramoto, Noriyoshi

Pflugers Archiv : European journal of physiology

2019 Volume 471, Issue 6, Page(s) 877–887

Abstract: Although ATP-sensitive ... ...

Abstract	Although ATP-sensitive K
MeSH term(s)	Animals ; Cell Line ; Insulin Secretion ; Mice, Inbred BALB C ; Potassium Channels, Inwardly Rectifying/metabolism ; rab GTP-Binding Proteins/metabolism
Chemical Substances	Kir6.2 channel ; Potassium Channels, Inwardly Rectifying ; Rab8a protein, mouse ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2019-01-10
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-018-02252-1
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Article ; Online: ZD0947, a sulphonylurea receptor modulator, detects functional sulphonylurea receptor subunits in murine vascular smooth muscle ATP-sensitive K

Yamamoto, Tadashi / Takahara, Kohei / Uchida, Keiichiro / Teramoto, Noriyoshi

European journal of pharmacology

2017 Volume 800, Page(s) 34–39

Abstract: In order to identify functional sulphonylurea receptor (SUR.x) subunits of native ATP-sensitive ... ...

Abstract	In order to identify functional sulphonylurea receptor (SUR.x) subunits of native ATP-sensitive K
MeSH term(s)	Animals ; Dihydropyridines/pharmacology ; Electrophysiological Phenomena/drug effects ; KATP Channels/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/physiology ; Portal Vein/drug effects ; Portal Vein/physiology ; Protein Subunits/metabolism ; Sulfonylurea Receptors/metabolism ; Vasoconstriction/drug effects
Chemical Substances	Dihydropyridines ; KATP Channels ; Protein Subunits ; Sulfonylurea Receptors ; ZD0947
Language	English
Publishing date	2017-04-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2017.02.023
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Article ; Online: Selective blocking effects of 4,9-anhydrotetrodotoxin, purified from a crude mixture of tetrodotoxin analogues, on NaV1.6 channels and its chemical aspects.

Teramoto, Noriyoshi / Yotsu-Yamashita, Mari

Marine drugs

2015 Volume 13, Issue 2, Page(s) 984–995

Abstract: Tetrodotoxin (TTX) is a potent neurotoxin found in a number of marine creatures including the pufferfish, where it is synthesized by bacteria and accumulated through the food chain. It is a potent and selective blocker of some types of voltage-gated Na+ ... ...

Abstract	Tetrodotoxin (TTX) is a potent neurotoxin found in a number of marine creatures including the pufferfish, where it is synthesized by bacteria and accumulated through the food chain. It is a potent and selective blocker of some types of voltage-gated Na+ channel (NaV channel). 4,9-Anhydrotetrodotoxin (4,9-anhydroTTX) was purified from a crude mixture of TTX analogues (such as TTX, 4-epiTTX, 6-epiTTX, 11-oxoTTX and 11-deoxyTTX) by the use of liquid chromatography-fluorescence detection (LC-FLD) techniques. Recently, it has been reported that 4,9-anhydroTTX selectively blocks the activity of NaV1.6 channels with a blocking efficacy 40-160 times higher than that for other TTX-sensitive NaV1.x channel isoforms. However, little attention has been paid to the molecular properties of the α-subunit in NaV1.6 channels and the characteristics of binding of 4,9-anhydroTTX. From a functional point of view, it is important to determine the relative expression of NaV1.6 channels in a wide variety of tissues. The aim of this review is to discuss briefly current knowledge about the pharmacology of 4,9-anhydroTTX, and provide an analysis of the molecular structure of native NaV1.6 channels. In addition, chemical aspects of 4,9-anhydroTTX are briefly covered.
MeSH term(s)	Animals ; Humans ; Mice ; Mice, Knockout ; NAV1.6 Voltage-Gated Sodium Channel/drug effects ; NAV1.6 Voltage-Gated Sodium Channel/genetics ; Sodium Channel Blockers/chemical synthesis ; Sodium Channel Blockers/pharmacology ; Tetrodotoxin/analogs & derivatives ; Tetrodotoxin/chemical synthesis ; Tetrodotoxin/pharmacology
Chemical Substances	NAV1.6 Voltage-Gated Sodium Channel ; Scn8a protein, mouse ; Sodium Channel Blockers ; anhydrotetrodotoxin (13072-89-4) ; Tetrodotoxin (4368-28-9)
Language	English
Publishing date	2015-02-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2175190-0
ISSN	1660-3397 ; 1660-3397
ISSN (online)	1660-3397
ISSN	1660-3397
DOI	10.3390/md13020984
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Article ; Online: Effects of ZD0947, a novel and potent ATP-sensitive K

Mori, Keisuke / Yamashita, Yoshio / Teramoto, Noriyoshi

European journal of pharmacology

2016 Volume 791, Page(s) 773–779

Abstract: The effects of ZD0947, a novel ATP-sensitive ... ...

Abstract	The effects of ZD0947, a novel ATP-sensitive K
MeSH term(s)	Dihydropyridines/pharmacology ; Dose-Response Relationship, Drug ; HEK293 Cells ; Humans ; Ion Channel Gating/drug effects ; KATP Channels/chemistry ; KATP Channels/metabolism ; Muscle, Smooth/metabolism ; Pinacidil/pharmacology ; Sulfonylurea Receptors/metabolism
Chemical Substances	Dihydropyridines ; KATP Channels ; Sulfonylurea Receptors ; ZD0947 ; Pinacidil (7B0ZZH8P2W)
Language	English
Publishing date	2016-11-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2016.09.038
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Article ; Online: Selective Blocking Effects of 4,9-Anhydrotetrodotoxin, Purified from a Crude Mixture of Tetrodotoxin Analogues, on NaV1.6 Channels and Its Chemical Aspects

Noriyoshi Teramoto / Mari Yotsu-Yamashita

Marine Drugs, Vol 13, Iss 2, Pp 984-

2015 Volume 995

Abstract	Tetrodotoxin (TTX) is a potent neurotoxin found in a number of marine creatures including the pufferfish, where it is synthesized by bacteria and accumulated through the food chain. It is a potent and selective blocker of some types of voltage-gated Na+ channel (NaV channel). 4,9-Anhydrotetrodotoxin (4,9-anhydroTTX) was purified from a crude mixture of TTX analogues (such as TTX, 4-epiTTX, 6-epiTTX, 11-oxoTTX and 11-deoxyTTX) by the use of liquid chromatography-fluorescence detection (LC-FLD) techniques. Recently, it has been reported that 4,9-anhydroTTX selectively blocks the activity of NaV1.6 channels with a blocking efficacy 40–160 times higher than that for other TTX-sensitive NaV1.x channel isoforms. However, little attention has been paid to the molecular properties of the α-subunit in NaV1.6 channels and the characteristics of binding of 4,9-anhydroTTX. From a functional point of view, it is important to determine the relative expression of NaV1.6 channels in a wide variety of tissues. The aim of this review is to discuss briefly current knowledge about the pharmacology of 4,9-anhydroTTX, and provide an analysis of the molecular structure of native NaV1.6 channels. In addition, chemical aspects of 4,9-anhydroTTX are briefly covered.
Keywords	4,9-anhydrotetrodotoxin ; LC-FLD techniques ; NaV1.6 channels ; tetrodotoxin ; Biology (General) ; QH301-705.5
Subject code	540
Language	English
Publishing date	2015-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Physiological roles of ATP-sensitive K+ channels in smooth muscle.

Teramoto, Noriyoshi

The Journal of physiology

2006 Volume 572, Issue Pt 3, Page(s) 617–624

Abstract: Potassium channels that are inhibited by intracellular ATP (ATP(i)) were first identified in ventricular myocytes, and are referred to as ATP-sensitive K+ channels (i.e. K(ATP) channels). Subsequently, K+ channels with similar characteristics have been ... ...

Abstract	Potassium channels that are inhibited by intracellular ATP (ATP(i)) were first identified in ventricular myocytes, and are referred to as ATP-sensitive K+ channels (i.e. K(ATP) channels). Subsequently, K+ channels with similar characteristics have been demonstrated in many other tissues (pancreatic beta-cells, skeletal muscle, central neurones, smooth muscle). Approximately one decade ago, K(ATP) channels were cloned and were found to be composed of at least two subunits: an inwardly rectifying K+ channel six family (Kir6.x) that forms the ion conducting pore and a modulatory sulphonylurea receptor (SUR) that accounts for several pharmacological properties. Various types of native K(ATP) channels have been identified in a number of visceral and vascular smooth muscles in single-channel recordings. However, little attention has been paid to the molecular properties of the subunits in K(ATP) channels and it is important to determine the relative expression of K(ATP) channel components which give rise to native K(ATP) channels in smooth muscle. The aim of this review is to briefly discuss the current knowledge available for K(ATP) channels with the main interest in the molecular basis of native K(ATP) channels, and to discuss their possible linkage with physiological functions in smooth muscle.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Animals ; Humans ; Ion Channel Gating/physiology ; Membrane Potentials/physiology ; Muscle Contraction/physiology ; Muscle, Smooth/physiology ; Potassium Channels/chemistry ; Potassium Channels/physiology
Chemical Substances	Potassium Channels ; mitochondrial K(ATP) channel ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2006-05-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2006.105973
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Article: Pharmacological Profile of U-37883A, a Channel Blocker of Smooth Muscle-Type ATP-Sensitive K Channels.

Teramoto, Noriyoshi

Cardiovascular drug reviews

2006 Volume 24, Issue 1, Page(s) 25–32

Abstract: U-37883A (PNU-37883A, guanidine; 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl hydrochloride) was originally developed as a potential diuretic with specific binding in kidney and vascular smooth muscle rather than in brain or pancreatic beta ... ...

Abstract	U-37883A (PNU-37883A, guanidine; 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl hydrochloride) was originally developed as a potential diuretic with specific binding in kidney and vascular smooth muscle rather than in brain or pancreatic beta cells. U-37883A inhibits ATP-sensitive K(+) channels (K(ATP) channels) in vascular smooth muscle at submicromolar concentrations whilst even at high concentrations (> or =10 microM) it has no inhibitory effect at pancreatic, cardiac or skeletal K(ATP) channels. Thus, it is generally thought that U-37883A is a selective inhibitor of vascular smooth muscle K(ATP) channels. Approximately one decade ago, K(ATP) channels were cloned and found to consist of at least two subunits: an inwardly-rectifying K(+) channel six family (K(ir)6.x; K(ir)6.1 and K(ir)6.2) which forms the ion conducting pore and a modulatory sulphonylurea receptor (SUR.x; SUR1, SUR2A, and SUR2B) that accounts for several pharmacological properties. It is generally believed that different combinations of K(ir)6.x and SUR.x determine the molecular properties of K(ATP) channels. Thus, K(ir)6.2/SUR1 channel represents the pancreatic beta-cell K(ATP) channel, K(ir)6.2/SUR2A channel is thought to represent the cardiac K(ATP) channel, whereas K(ir)6.1/SUR2B channel is likely to represent the vascular smooth muscle K(ATP) channel. Recent molecular studies have shown that U-37883A selectively suppresses the activity of recombinant K(ATP) channels which contain K(ir)6.1 subunits in the channel pore unit. It was thus thought that U-37883A was a selective pharmacological tool which could be used to investigate the activity of vascular smooth muscle K(ATP) channels. However, due to its multiple pharmacological actions on several ion channels and poor tissue selectivity, U-37883A should not be viewed as a selective blocker of smooth muscle K(ATP) channels.
MeSH term(s)	Adamantane/analogs & derivatives ; Adamantane/pharmacology ; Animals ; Diuretics/pharmacology ; Morpholines/pharmacology ; Muscle, Smooth, Vascular/drug effects ; Potassium Channel Blockers/chemistry ; Potassium Channel Blockers/pharmacology ; Potassium Channels/drug effects
Chemical Substances	Diuretics ; Morpholines ; Potassium Channel Blockers ; Potassium Channels ; U 37883A (57568-80-6) ; Adamantane (PJY633525U)
Language	English
Publishing date	2006
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645099-4
ISSN	0897-5957
ISSN	0897-5957
DOI	10.1111/j.1527-3466.2006.00025.x
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Article ; Online: L-type Ca2+ channel sparklets revealed by TIRF microscopy in mouse urinary bladder smooth muscle.

Sidaway, Peter / Teramoto, Noriyoshi

PloS one

2014 Volume 9, Issue 4, Page(s) e93803

Abstract: Calcium is a ubiquitous second messenger in urinary bladder smooth muscle (UBSM). In this study, small discrete elevations of intracellular Ca(2+), referred to as Ca(2+) sparklets have been detected in an intact detrusor smooth muscle electrical ... ...

Abstract	Calcium is a ubiquitous second messenger in urinary bladder smooth muscle (UBSM). In this study, small discrete elevations of intracellular Ca(2+), referred to as Ca(2+) sparklets have been detected in an intact detrusor smooth muscle electrical syncytium using a TIRF microscopy Ca(2+) imaging approach. Sparklets were virtually abolished by the removal of extracellular Ca(2+) (0.035 ± 0.01 vs. 0.23 ± 0.07 Hz/mm(2); P<0.05). Co-loading of smooth muscle strips with the slow Ca(2+) chelator EGTA-AM (10 mM) confirmed that Ca(2+) sparklets are restricted to the cell membrane. Ca(2+) sparklets were inhibited by the calcium channel inhibitors R-(+)-Bay K 8644 (1 μM) (0.034 ± 0.02 vs. 0.21 ± 0.08 Hz/mm(2); P<0.05), and diltiazem (10 μM) (0.097 ± 0.04 vs. 0.16 ± 0.06 Hz/mm(2); P<0.05). Ca(2+) sparklets were unaffected by inhibition of P2X1 receptors α,β-meATP (10 μM) whilst sparklet frequencies were significantly reduced by atropine (1 μM). Ca(2+) sparklet frequency was significantly reduced by PKC inhibition with Gö6976 (100 nM) (0.030 ± 0.01 vs. 0.30 ± 0.1 Hz/mm(2); P<0.05), demonstrating that Ca(2+) sparklets are PKC dependant. In the presence of CPA (10 μM), there was no apparent change in the overall frequency of Ca(2+) sparklets, although the sparklet frequencies of each UBSM became statistically independent of each other (Spearman's rank correlation 0.2, P>0.05), implying that Ca(2+) store mediated signals regulate Ca(2+) sparklets. Under control conditions, inhibition of store operated Ca(2+) entry using ML-9 (100 μM) had no significant effect. Amplitudes of Ca(2+) sparklets were unaffected by any agonists or antagonists, suggesting that these signals are quantal events arising from activation of a single channel, or complex of channels. The effects of CPA and ML-9 suggest that Ca(2+) sparklets regulate events in the cell membrane, and contribute to cytosolic and sarcoplasmic Ca(2+) concentrations.
MeSH term(s)	Animals ; Calcium Channels, L-Type/physiology ; Calcium Signaling/physiology ; Male ; Mice ; Microscopy, Fluorescence/methods ; Muscle, Smooth/physiology ; Protein Kinase C/metabolism ; Urinary Bladder/physiology
Chemical Substances	Calcium Channels, L-Type ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	2014-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0093803
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Article ; Online: L-type Ca2+ channel sparklets revealed by TIRF microscopy in mouse urinary bladder smooth muscle.

Peter Sidaway / Noriyoshi Teramoto

PLoS ONE, Vol 9, Iss 4, p e

2014 Volume 93803

Abstract	Calcium is a ubiquitous second messenger in urinary bladder smooth muscle (UBSM). In this study, small discrete elevations of intracellular Ca(2+), referred to as Ca(2+) sparklets have been detected in an intact detrusor smooth muscle electrical syncytium using a TIRF microscopy Ca(2+) imaging approach. Sparklets were virtually abolished by the removal of extracellular Ca(2+) (0.035 ± 0.01 vs. 0.23 ± 0.07 Hz/mm(2); P<0.05). Co-loading of smooth muscle strips with the slow Ca(2+) chelator EGTA-AM (10 mM) confirmed that Ca(2+) sparklets are restricted to the cell membrane. Ca(2+) sparklets were inhibited by the calcium channel inhibitors R-(+)-Bay K 8644 (1 μM) (0.034 ± 0.02 vs. 0.21 ± 0.08 Hz/mm(2); P<0.05), and diltiazem (10 μM) (0.097 ± 0.04 vs. 0.16 ± 0.06 Hz/mm(2); P<0.05). Ca(2+) sparklets were unaffected by inhibition of P2X1 receptors α,β-meATP (10 μM) whilst sparklet frequencies were significantly reduced by atropine (1 μM). Ca(2+) sparklet frequency was significantly reduced by PKC inhibition with Gö6976 (100 nM) (0.030 ± 0.01 vs. 0.30 ± 0.1 Hz/mm(2); P<0.05), demonstrating that Ca(2+) sparklets are PKC dependant. In the presence of CPA (10 μM), there was no apparent change in the overall frequency of Ca(2+) sparklets, although the sparklet frequencies of each UBSM became statistically independent of each other (Spearman's rank correlation 0.2, P>0.05), implying that Ca(2+) store mediated signals regulate Ca(2+) sparklets. Under control conditions, inhibition of store operated Ca(2+) entry using ML-9 (100 μM) had no significant effect. Amplitudes of Ca(2+) sparklets were unaffected by any agonists or antagonists, suggesting that these signals are quantal events arising from activation of a single channel, or complex of channels. The effects of CPA and ML-9 suggest that Ca(2+) sparklets regulate events in the cell membrane, and contribute to cytosolic and sarcoplasmic Ca(2+) concentrations.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article: [Molecular and electrophysiological investigation of ATP-sensitive K+ channels in lower urinary tract function: the aims for clinical treatment of unstable detrusor].

Teramoto, Noriyoshi

Nihon yakurigaku zasshi. Folia pharmacologica Japonica

2003 Volume 121, Issue 5, Page(s) 317–324

Abstract: It is a common sequelae of bladder outlet obstruction caused by benign prostatic hyperplasia in adult males and gives rise to significant bladder dysfunction such as frequency and urgency of micturition. The unstable detrusor contractions may lead to ... ...

Abstract	It is a common sequelae of bladder outlet obstruction caused by benign prostatic hyperplasia in adult males and gives rise to significant bladder dysfunction such as frequency and urgency of micturition. The unstable detrusor contractions may lead to urge incontinence. Since it has been reported that experimentally-induced bladder instability can be abolished by ATP-sensitive K+ channel (KATP channel) openers, various types of detrusor-selective KATP channels have been newly synthesized, targeting KATP channels in urinary bladder. Thus, the significant differences in molecular and pharmacological properties of KATP channels between urinary bladder and urethra hold out some hope for the development of tissue-selective KATP channel openers for urge urinary incontinence, and detrusor-selective KATP channel openers should be screened against urethral as well as vascular smooth muscle. In functional expression experiments, pharmacological and electrophysiological studies have reported that SUR1/Kir6.2 represents the pancreatic beta-cell KATP channel and that SUR2A/Kir6.2 is thought to represent the cardiac KATP channel, whereas SUR2B/Kir6.1 represents the smooth muscle-type KATP channel. In general, the smooth muscle type-KATP channel is (i) of a relatively small conductance (about 20 pS under quasi-physiological conditions, approximately 40 pS in symmetrical 140 mM K+ conditions), (ii) intracellular Ca(2+)-insensitive, (iii) inhibited by intracellular ATP, (iv) abolished by glibenclamide at a submicromolar concentration, and (v) reactivated by intracellular nucleoside diphosphates (NDPs). There has been no report concerning the properties of KATP channels in human detrusor by use of single-channel recordings. We would like to introduce our recent evidence of novel synthesized detrusor-selective KATP channel openers and properties of KATP channels in the lower urinary tract.
MeSH term(s)	Adenosine Triphosphate/physiology ; Animals ; Humans ; Male ; Potassium Channels/drug effects ; Potassium Channels/physiology ; Urinary Bladder/physiology ; Urinary Incontinence/physiopathology
Chemical Substances	Potassium Channels ; Adenosine Triphosphate (8L70Q75FXE)
Language	Japanese
Publishing date	2003-05-01
Publishing country	Japan
Document type	English Abstract ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1097532-9
ISSN	1347-8397 ; 0015-5691
ISSN (online)	1347-8397
ISSN	0015-5691
DOI	10.1254/fpj.121.317
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