Relationship between Cyclic Nucleotide Levels and 5-Methyl-6-(4-pyridyl)-2H-1,4-thiazin-3 (4H)-one (ZSY-27), a New Positive Inotropic Agent with a Vasodilatory Action, -Induced Relaxation of Rabbit Thoracic Aorta
スポンサーリンク
概要
- 論文の詳細を見る
The aim of this investigation was to substantiate the hypothesis that the vasorelaxant effects of 5-methyl-6-(4-pyridyl)-2H-1,4-thiazin-3 (4H)-one (ZSY-27) are mediated by accumulation of intracellular cyclic nucleotides as a consequence of inhibition of cyclic nucleotide phosphodiesterase activity. Both activities of adenosine 3', 5'-monophosphate-phosphodiesterase (cAMP-PDE) in the presence of ethylene glycol-bis (β-aminoethyl ether) N, N, N', N'-tetraacetic acid (EGTA) and guanosine 3', 5'-monophosphate-phosphodiesterase (cGMP-PDE) in the presence of calcium-calmodulin from rabbit thoracic aorta were inhibited in a concentration-dependent manner by ZSY-27 (10^<-5>-10^<-3>M). The IC_<50> values for ZSY-27 on cAMP-and cGMP-PDE activity were 2.1×10^<-4> and 8.8×10^<-4>M, respectively. Furthermore, ZSY-27 antagonized competitively cAMP-PDE (K_i=1.9×10^<-4>M). On the other hand, ZSY-27 exhibited a mixed-type inhibitory pattern, with reduction of both maximum velocity and affinity for the substrate of the cGMP-PDE, with a K_i value of 1.0×10^<-3>M. Spontaneous myogenic tone of rabbit thoracic aorta was significantly attenuated from 1 min after addition of ZSY-27 (3×10^<-4>M). Contents of cAMP and cGMP were significantly increased from 1 and 3 min after addition of ZSY-27,respectively. Temporally, relaxant effects of ZSY-27 were associated with increases of cAMP content, but not with that of cGMP content. Furthermore, the relaxant effect of ZSY-27 on the phenylephrine-induced contraction was not affected by the pretreatment with nitroprusside. These results support the hypothesis that elevation of cAMP level via inhibition of cAMPPDE activity is intimately involved in the mechanism of vasorelaxation produced by ZSY-27.
- 公益社団法人日本薬学会の論文
著者
-
TAKAYANAGI Issei
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences
-
HISAYAMA Tetsuhiro
Department of Pharmacology, Faculty of Pharmaceutical Scienses, The University of Tokushima
-
Takayanagi Issei
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences University Of Tokyo:(correspo
-
Takayanagi I
Department Of Chemical Pharmacology Toho University School Of Pharmaceutical Sciences
-
YOSHIOKA Kimitomo
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences
-
Hisayama T
Department Of Chemical Pharmacology Toho University School Of Pharmaceutical Sciences
-
Hisayama Tetsuhiro
Department Of Chemical Pharmacology Toho University School Of Pharmaceutical Sciences
-
Yoshioka K
Research Laboratory Zenyaku Kogyo Co. Ltd.
-
Yoshioka Kimitomo
Department Of Chemical Pharmacology Toho University School Of Pharmaceutical Sciences:(present Addre
関連論文
- The Characteristics of Endothelin Receptor Subtypes on Muscle Contraction and Neuro-transmission in Rat Vas Deferens
- Effect of Endothelin-1 (1-31) on Human Mesangial Cell Proliferation
- THE ACTIONS OF SODIUM NITROPRUSSIDE AND DILTIAZEM ON CALCIUM-, POTASSIUM- AND HISTAMINE-INDUCED CONTRACTILE RESPONSES IN ISOLATED RABBIT BASILAR ARTERY, AORTA, TAENIA COLI AND TRACHEAL SMOOTH MUSCLE
- EFFECTS OF NICOTINE IN THE ISOLATED AIRWAY SMOOTH MUSCLE PREPARATIONS
- PHARMACOLOGICAL CHARACTERIZATION OF IONOPHORE X537A-INDUCED CONTRACTILE RESPONSES IN ISOLATED RABBIT TAENIA COLI AND AORTA
- A POSSIBLE MECHANISM OF ACTION OF A BETA-ADRENERGIC PARTIAL AGONIST (CARTEOLOL) IN GUINEA PIG TAENIA CAECUM
- Characteristics of Ca^ Oscillations in Ileal Longitudinal Muscle Cells of Guinea Pig
- Differences of Antagonism for a Selective α_-Adrenoceptor Antagonist BMY 7378 in the Rabbit Thoracic Aorta and Iliac Artery
- The β_2- and β_3-Adrenoceptor-Mediated Relaxation Induced by Isoprenaline and Salbutamol in Guinea Pig Taenia Caecum
- Signal Transduction Pathway Involved in β_3 - Adrenoceptor - Mediated Relaxation in Guinea Pig Taenia Caecum
- GREATER TENSION IS DEVELOPED AT THE SAME LEVEL OF CYTOSOLIC Ca^ CONCENTRATION IN THE PRESENCE OF CLONIDINE, AN ADRENERGIC PARTIAL AGONIST, THAN IN THE PRESENCE OF NOREPINEPHRINE
- EFFECTS OF AGING ON ALPHA-1 AND-2 ADRENOCEPTOR MECHANISMS IN SMOOTH MUSCLES
- ALPHA_1-ADRENOCEPTOR MECHANISM AND AGING
- INTERACTIONS OF BEFUNOLOL, A BETA-ADRENERGIC PARTIAL AGONIST, AND ITS DERIVATIVES WITH HIGH AND LOW AFFINITY SITES IN BETA-ADRENOCEPTORS
- INTERACTION OF DYNORPHIN DERIVATIVE CONTAINING 3-NITRO-2-PYRIDINESULFENYL (Npys) GROUP WITH OPIOID RECEPTORS
- Effects of a New Positive Inotropic Agent with a Vasodilatory Action, 5-Methyl-6-(4-pyridyl)-2H-1,4-thiazin-3 (4H)-one (ZSY-27), on Calcium-Movement and Mechanical Response in Rabbit Thoracic Aorta
- EFFECTS OF SMOOTH MUSCLE STIMULANTS ON I-ISOPRENALINE-β-ADRENOCEPTOR INTERACTION IN TAENIA FROM GUINEA PIG CAECUM
- CHARACTERIZATION OF NOREPINEPHRINE-INDUCED CONTRACTILE RESPONSE IN ISOLATED RABBIT BASILAR ARTERY
- PHARMACOLOGICAL ACTIONS OF LEUKOTRIENES C_4,D_4 AND E_4 ON GUINEA PIG ISOLATED TAENIA CAECUM AS A PREPARATION TO STUDY LEUKOTRIENES
- THE ACTIONS OF D 600, ASPAMINOL AND PAPAVERINE ON CALCIUM-, POTASSIUM- AND HISTAMINE-INDUCED CONTRACTIONS OF ISOLATED RABBIT BASILAR ARTERY, AORTA, TAENIA COLI AND TRACHEAL SMOOTH MUSCLE
- Relationship between Cyclic Nucleotide Levels and 5-Methyl-6-(4-pyridyl)-2H-1,4-thiazin-3 (4H)-one (ZSY-27), a New Positive Inotropic Agent with a Vasodilatory Action, -Induced Relaxation of Rabbit Thoracic Aorta
- Effects of a New Positive Inotropic Agent with a Vasodilatory Action, 5-Methyl-6-(4-pyridyl)-2H-1,4-thiazin-3 (4H)-one (ZSY-27), on Agonists-Induced Contractions in the Isolated Rabbit Thoracic Aorta
- PHARMACOLOGICAL MULTIPLICITY OF RECEPTOR SITES FOR THE MAMMALIAN TACHYKININS IN RABBIT IRIS SPHINCTER MUSCLE
- EFFECTS OF A COMBINED STOMACHIC AND ITS INGREDIENTS ON RABBIT STOMACH MOTILITY IN SITU
- CALCIUM IONS AND RELAXATION OF INTESTINAL SMOOTH MUSCLE INDUCED BY PAPAVERINE AND ASPAMINOL
- DOPAMINE AND ITS ANTAGONISTS ON MOLLUSCAN SMOOTH MUSCLE
- DOPAMINE RECEPTOR IN ANTERIOR BYSSUS RETRACTOR MUSCLE OF MYTILUS EDULIS
- INHIBITORY ALPHA-ADRENERGIC ACTION OF PHENYLEPHRINE IN GUINEA PIG TAENIA CAECUM
- NONSPECIFIC INHIBITORY ACTION OF CHINOFORM ON GASTROINTESTINE
- INTERACTION OF MORPHINE-EPOXIDE WITH MULTIPLE OPIATE RECEPTORS
- INTERACTION OF MORPHINE AND CODEINE-EPOXIDES WITH OPIATE RECEPTOR
- SOME PHARMACOLOGICAL PROPERTIES OF MORPHINE-7,8-OXIDE (MORPHINE EPOXIDE)
- PHARMACOLOGICAL PROPERTIES OF CODEINE-7, 8-OXIDE (CODEINE EPOXIDE), A NEW METABOLITE OF CODEINE
- EFFECTS OF EPOXIDES OF HEROIN, MORPHINE AND CODEINE ON THE ELECTRICALLY STIMULATED GUINEA PIG ILEUM
- EFFECTS OF COCAINE ON Ca-MOBILITY IN MICROSOMAL FRACTION FROM RAT VAS DEFERENS
- EFFECTS OF ACETYLCHOLINE AND HISTAMINE ON MECHANICAL ACTIVITY OF RABBIT TAENIA COLI, Ca-INCORPORATION AND Ca-RELEASE IN ITS MICROSOMAL FRACTION
- NONSPECIFIC RELAXATION OF INTESTINAL SMOOTH MUSCLE INDUCED BY ANTISPASMODICS AND MOVEMENT OF CALCIUM IONS
- DRUG-INDUCED SMOOTH MUSCLE CONTRACTION WITH NO CHANGE IN THE LEVEL OF CYCLIC GMP
- INHIBITION OF Ca-MOVEMENT AND MECHANICAL MOVEMENT IN RABBIT TAENIA COLI BY A SMOOTH MUSCLE RELAXANT (SULOCTIDIL)
- EFFECTS OF SMOOTH MUSCLE RELAXANT (ASPAMINOL) ON Ca-UPTAKE BY MITOCHONDRIAL AND MICROSOMAL FRACTIONS FROM RAT UTERUS
- EFFECTS OF NONSPECIFIC SMOOTH MUSCLE RELAXANTS ON CALCIUM-UPTAKE BY MICROSOMAL FRACTION AND THEIR INHIBITORY ACTION IN RABBIT TAENIA COLI
- EFFECTS OF CALCIUM IONS AND MAGNESIUM IONS ON 5-HYDROXYTRYPTAMINE-RECEPTOR INTERACTION
- EFFECTS OF NONSPECIFIC SMOOTH MUSCLE RELAXANTS ON GLYCOGEN PHOSPHORYLASE ACTIVITY IN DEPOLARIZED TAENIA CAECUM OF GUINEA PIG
- EFFECTS OF NONSPECIFIC SMOOTH MUSCLE RELAXANTS ON TISSUE CONCENTRATIONS OF HIGH ENERGY PHOSPHATES AND MECHANICAL ACTIVITY OF NORMAL POLARIZED AND DEPOLARIZED INTESTINAL SMOOTH MUSCLES FROM GUINEA PIG
- ANTIPHOSPHODIESTERASE ACTIVITY AND NONSPECIFIC SMOOTH MUSCLE RELAXATION TESTED ON INTESTINAL SMOOTH MUSCLES
- EXTERNAL CALCIUM IONS AND MECHANICAL RESPONSES OF THE AORTA ISOLATED FROM THE CHOLESTEROL-FED RABBIT
- RELAXING ACTION OF SYNTHETIC ANTISPASMODICS ON THE INTESTINAL SMOOTH MUSCLE OF GUINEA PIG
- INTRACELLULAR CYCLIC ADENOSINE 3, 5-MONOPHOSPHATE AND RELAXING EFFECTS OF ISOPRENALINE AND PAPAVERINE ON SMOOTH MUSCLE OF INTESTINE
- POSSIBLE MECHANISMS OF STIMULATORY ACTION OF PAPAVERINE ON CALCIUM-UPTAKE BY RAT UTERINE MICROSOMAL FRACTION
- EFFECTS OF ANTI-ASTHMATIC DRUGS ON AIRWAY RESISTANCE AND PLASMA LEVEL OF CYCLIC AMP IN GUINEA PIG
- RELATIONSHIP BETWEEN THE Ba-INDUCED CONTRACTION AND CYCLIC AMP LEVELS IN THE ISOLATED LONGITUDINAL SMOOTH MUSCLE FROM GUINEA PIG ILEUM
- A DUAL ACTION OF MUSCARINIC PARTIAL AGONISTS ON PUPIL SIZE OF RABBIT
- A DIFFERENCE IN PHARMACOLOGICAL PROPERTIES OF HISTAMINE RECEPTORS IN RABBIT AORTA AND BASILAR ARTERY
- EFFECTS OF NONSPECIFIC SMOOTH MUSCLE RELAXANTS AND Ca-BLOCKER ON Ca-RELEASE AND Ca-BINDING IN MICROSOMAL FRACTIONS FROM RABBIT TAENIA COLI
- ACTIONS OF PAPAVERINE, ASPAMINOL AND BILE SALTS AND INTRACELLULAR CYCLIC AMP LEVEL
- COMPARISON OF ACTIONS OF PAPAVERINE, ASPAMINOL AND ISOPRENALINE ON ISOLATED RAT UTERUS
- ANTI-OXYTOCIN ACTIONS OF PAPAVERINE, ASPAMINOL AND ISOPRENALINE ON THE RAT UTERUS AND INTRACELLULAR CYCLIC ADENOSINE 3, 5-MONOPHOSPHATE LEVEL
- INHIBITORY ACTION OF 2-(1,2-BENZISOXAZOL-3-YL)-3-[2-(2-PIPERIDINOETHOXY)PHENYL]ACRYLONITRILE (SX-284) ON ACETYLCHOLINE RELEASE FROM VAGUS NERVE IN GUINEA PIG ILEUM
- RELATIONSHIP BETWEEN SYNAPTOSOMAL CALCIUM UPTAKE AND ANTINOCICEPTIVE ACTION OF MORPHINE
- EFFECT OF 1, 1-DIPHENYL-3-PIPERIDINOBUTANOL HYDROCHLORIDE (ASPAMINOL) ON THE STIMULI-INDUCED CALCIUM UPTAKE IN RAT BRAIN SYNAPTOSOMES
- EFFECTS OF MORPHINE, CODEINE AND CODEINE-EPOXIDE ON CALCIUM UPTAKE INTO THE SYNAPTOSOMES ISOLATED FROM NAIVE AND TOLERANT RATS
- EFFECT OF MORPHINE ON THE STIMULI-INDUCED CALCIUM UPTAKE INTO SYNAPTOSOMES ISOLATED FROM MORPHINE-TOLERANT RATS
- SPECIFIC 3H-HALOPERIDOL BINDING TO DOPAMINE RECEPTORS IN THE ANTERIOR BYSSUS RETRACTOR MUSCLE OF MYTILUS EDULIS
- EFFECTS OF SOME ERGOT ALKALOIDS ON DOPAMINE RECEPTORS OF MOLLUSCAN SMOOTH MUSCLE
- MEAHANISM OF ACTION OF NICOTINE IN ISOLATED URINARY BLADDER FROM GUINEA-PIG
- ACTIONS OF DIBUTYRYL CYCLIC ADENOSINE MONO-PHOSPHATE, PAPAVERINE AND ISOPRENALINE ON THE INTESTINAL SMOOTH MUSCLE
- ACTION OF DIBUTYRYL CYCLIC ADENOSINE MONOPHOSPHATE ON THE INTESTINAL SMOOTH MUSCLE
- EFFECT OF N6, 2-O-DIBUTYRYL 35-CYCLIC ADENOSINE MONOPHOSPHATE, 3, 5, -CYCLIC ADENOSINE MONOPHOSPHATE AND ADENOSINE TRIPHOSPHATE ON ACETYLCHOLINE OUTPUT FROM CHOLINERGIC NERVES IN GUINEA PIG ILEUM
- EFFECTS OF A REDUCTION IN EXTERNAL SODIUM ION CONCENTRATION ON ACTIONS OF SOME SMOOTH MUSCLE STIMULANTS
- BETA-ADRENOCEPTORS IN THE GUINEA PIG TREATED WITH EGG-ALBUMIN
- THE EFFECTS OF CAFFEINE AND IMIDAZOLE ON THE ACTIONS OF BETA- AND ALPHA-ADRENERGIC STIMULANTS, PAPAVERINE AND CYCLIC 3, 5-AMP
- POSSIBLE MECHANISMS OF A NEW TYPE OF ANTISPASMODIC DRUG, BTM-1042(CIS-(-)-2, 3-DIHYDRO-3-(4-METHYL-PIPERAZINYL)METHYL-2-PHENYL-1, 5-BENZOTHIAZEPIN-4(5H)-ONE DIHYDROCHLORIDE)
- A NEW PARASYMPATHOMIMETIC AGENT: 1-METHYL-5-CHLOROINDOLINE METHYLBROMIDE
- A RECEPTOR RESERVE OF THE ALPHA-INHIBITORY RECEPTOR FOR ALPHA-ADRENOCEPTOR STIMULANTS IN THE TAENIA CAECUM OF GUINEA PIG
- ACTIVATION OF GUANYLATE CYCLASE AS SECONDARY REACTION FOLLOWING INCREASE IN INTRACELLULAR Ca ION CONCENTRATIONS
- RELATIONSHIP BETWEEN INTRINSIC ACTIVITY OF β-ADRENOCEPTOR AGONIST AND AMOUNT OF SPARE RECEPTORS IN GUINEA PIG TAENIA CAECUM
- A POSSIBLE MECHANISM OF A NEW ANTISPASMODIC DRUG, 2-(1, 2-BENZISOXAZOL-3-YL)-3-[2-(2-PI PER IDINOETHOXY) PHENYL]ACRYLONITRILE (SX-284)
- PHARMACOLOGICAL PROPERTIES OF ACETYLCHOLINE RECEPTOR IN MOLLUSCAN SMOOTH MUSCLE
- THE ACTION OF DIBUTYRYL CYCLIC GMP (N2-2 O-DIBUTYRYL CYCLIC GUANOSINE-3, 5-MONO-PHOSPHATE) ON THE ILEUM OF GUINEA PIG
- EFFECT OF ACETYLCHOLINE ON DESENSITIZATION OF ISOLATED RAT TRACHEA TO 5-HYDROXYTRYPTAMINE —A POSSIBLE ALLOSTERIC INTERACTION BETWEEN DRUG RECEPTORS
- INTERACTIONS OF SOME PARTIAL AGONISTS WITH BETAADRENOCEPTOR IN GUINEA-PIG TAENIA CAECUM
- CALCIUM-INDUCED STIMULATION OF 45-CALCIUM-EFFLUX IN SMOOTH MUSCLE MICROSOMES
- EFFECTS OF ACETYLCHOLINE RELEASING DRUGS ON ELECTRICAL ACTIVITIES OBTAINED FROM AUERBACHS PLEXUS IN THE GUINEA PIG ILEUM
- PHARMACOLOGICAL PROPERTIES OF ELECTRICAL ACTIVITIES OBTAINED FROM NEURONS IN AUERBACHS PLEXUS
- BETA-ADRENERGIC BLOCKING ACTION OF RUTHENIUM RED
- MECHANISM OF ACTION OF RYANODINE AND REQUIREMENT OF OPERATION OF Ca-INDUCED Ca RELEASE FOR ONSET OF THE DRUG'S ACTION IN MAMMALIAN SMOOTH MUSCLE
- EFFECTS OF PHENOBARBITAL ON PLASMA CONCENTRATION OF PHENYTOIN AND MORTALITY OF MICE TREATED WITH PHENYTOIN AFTER ELECTROSHOCK
- Effects of Morphine, Clonidine and Papaverine on Synaptosomal 45Ca Uptake and Antinociceptive Action in Rats
- PHYSIOLOGICAL CALCIUM ION CONCENTRATION AND A CHOLINERGIC DRUG ON ACTIVITY OF PARTICULATE GUANYLATE CYCLASE IN GUINEA PIG TAENIA CAECUM
- A POSSIBLE MECHANISM FOR THE OCCURRENCE OF THE NON-SPECIFIC POTENTIATION IN THE DENERVATED SKELETAL MUSCLE OF THE RAT
- EFFECTS OF SOME DIVALENT CATIONS ON THE DENERVATED SKELETAL MUSCLE OF THE RAT
- A DIFFERENCE IN PHARMACOLOGICAL ACTION OF R (+) AND S (-) ISOMERS OF BEFUNOLOL, BETA-ADRENOCEPTOR BLOCKER
- INTERACTION OF THE PARTIAL AGONISTS WITH BETA-ADRENOCEPTOR IN GUINEA-PIG TAENIA CAECUM
- BETA-ADRENOCEPTOR MECHANISMS IN GUINEA PIG TAENIA CAECUM
- RELATIONSHIP BETWEEN THE LEVELS OF INTRACELLULAR CYCLIC NUCLEOTIDES AND MECHANICAL RESPONSES INDUCED BY DRUGS
- Difference in mode of action of alpha1-adrenoceptor antagonists on some vascular smooth muscles and efficacy.
- A difference in mode of antagonism between optical isomers of a potent selective alpha1-adrenoceptor blocker (YM-12617) and norepinephrine in isolated rabbit iris dilator and aorta.
- A difference in alpha-adrenoceptor mechanisms in vasa deferential isolated from young and old rats.
- THE EFFECTS OF EXTERNAL DIVALENT CATIONS ON HISTAMINE-RECEPTOR INTERACTION
- Pharmacological Characterization of Contractile Responses Induced by .ALPHA.1-Agonists, Norepinephrine and Clonidine, by Selective Antagonists of Their Subtypes in Rabbit Thoracic Aorta.