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Dive into the research topics where Ikunobu Muramatsu is active.

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Featured researches published by Ikunobu Muramatsu.


British Journal of Pharmacology | 1975

γ‐AMINOBUTYRIC ACID RECEPTOR ON VASCULAR SMOOTH MUSCLE OF DOG CEREBRAL ARTERIES

Motohatsu Fujiwara; Ikunobu Muramatsu; Shoji Shibata

γ‐Aminobutyric acid (GABA) had a relaxant effect on dog cerebral arteries which was blocked only by picrotoxin, a known antagonist of GABA receptors. Other agents, adrenoceptor and ganglion blocking agents, atropine, reserpine, tetrodotoxin and ouabain, had no effect on the inhibitory action suggesting the existence of GABA receptors in the vascular smooth muscle of dog cerebral arteries.


Naunyn-schmiedebergs Archives of Pharmacology | 1982

Pharmacological characterization of the alpha adrenoceptors of the dog basilar artery

Yoshihiko Sakakibara; Motohatsu Fujiwara; Ikunobu Muramatsu

SummaryThe effects of alpha adrenoceptor agonists and antagonists on the postsynaptic alpha receptors were examined in the dog basilar, mesenteric and renal arteries and the type of alpha adrenoceptors present was characterized. In the basilar artery, noradrenaline, clonidine and phenylephrine produced almost the same maximal contraction, the pD2 values being 6.51±0.11, 5.49±0.16 and 5.65±0.13, respectively. Yohimbine (1–3×10−8 M) inhibited the contractile responses to noradrenaline and clonidine competitively and the response to phenylephrine noncompetitively. Corynanthine (10−6 M) had no effect on such contractile responses. In the mesenteric and renal arteries, the maximal responses to noradrenaline and phenylephrine were markedly greater than those to clonidine. Yohimbine (10−7–10−5 M) and corynanthine (10−7–10−5 M) both antagonized noradrenaline competitively in these vessels. In the basilar, mesenteric and renal arteries preloaded with 3H-noradrenaline, 3H-efflux induced by electrical transmural stimulation was attenuated by clonidine (10−10–10−7 M), while phenylephrine (10−10–10−8 M) was without effect. Yohimbine at considerably lower concentrations than corynanthine increased the 3H-efflux clicited by electrical stimulation. These results indicate that presynaptic and postsynaptic alpha receptors of the dog basilar artery are largely alpha2 in contrast to those of peripheral arteries.


British Journal of Pharmacology | 2002

Distribution of alpha-1 adrenoceptor subtypes in RNA and protein in rabbit eyes

Fumiko Suzuki; Takanobu Taniguchi; Seigo Nakamura; Yoshio Akagi; Chikara Kubota; Makoto Satoh; Ikunobu Muramatsu

We investigated subtypes of alpha‐1 adrenoceptor (AR) in rabbit ocular tissues using reverse transcription‐polymerase chain reaction (RTu2003–u2003PCR), in situ hybridization (ISH) and binding studies. Competitive RTu2003–u2003PCR assays specific for the subtypes of alpha‐1 AR revealed that the mRNA expression of alpha‐1a AR was dominant, and that of each alpha‐1b and alpha‐1d was less than 10% and 0.5% of total alpha‐1 ARs mRNA, respectively, in the iris, ciliary body, choroid and retina. In alpha‐1a AR splice isoform‐specific RTu2003–u2003PCR assays, we found a distinct proportion of each isoform mRNA in the iris, ciliary body and choroid. The results of the ISH assays for alpha‐1a AR subtype showed that hybridization signals were clearly observed in the iris dilator muscle and in the epithelium of the ciliary processes. In binding studies, alpha‐1A AR was a dominant subtype in the iris, choroid and retina in contrast to the ciliary body that had more alpha‐1B than alpha‐1A AR subtype at protein level.


British Journal of Pharmacology | 2004

Alpha‐1 adrenoceptors: evaluation of receptor subtype‐binding kinetics in intact arterial tissues and comparison with membrane binding

Takashi Tanaka; Li Zhang; Fumiko Suzuki; Ikunobu Muramatsu

The binding kinetics of [3H]‐prazosin were measured using intact segments of rat tail artery (RTA) and thoracic aorta (RAO), and the data were compared with those obtained using a conventional membrane ligand‐binding method. In intact RTA and RAO segments, [3H]‐prazosin bound reversibly in a time‐dependent and receptor‐specific manner at 4°C to alpha‐1 adrenoceptors (ARs) of the plasma membrane, with affinities (pKD: 9.5 in RTA; 9.9 in RAO) that were in agreement with values estimated by a conventional membrane ligand‐binding method. However, nonspecific binding was considerably higher in RAO than RTA, failing to detect clearly the specific binding at high concentrations (>300 pM) of [3H]‐prazosin in binding experiments with RAO segments and membranes. The abundance of receptor in the RTA and RAO (Bmax mg−1 of total tissue protein), estimated using the tissue segment‐binding approach (527±14 fmol mg−1 for RTA; 138±4 fmol mg−1 for RAO), was about 25‐fold higher than values estimated using a conventional membrane‐binding method (22±5 fmol mg−1 for RTA; 5±1 fmol mg−1 for RAO). Binding competition experiments using intact tissue segments or membranes derived from RTA tissue yielded comparable data, indicating a coexistence of alpha‐1A AR (high affinity for prazosin, KMD‐3213 and WB4101 and low affinity for BMY 7378) and alpha‐1B AR (high affinity for prazosin but low affinity for KMD‐3213, WB4101 and BMY 7378). In RAO tissue, careful evaluation of the tissue segment‐binding assay revealed the coexpression of alpha‐1B AR (high affinity for prazosin, but low affinity for KMD‐3213 and BMY 7378) and alpha‐1D AR (high affinity for prazosin and BMY 7378, but low affinity for KMD‐3213), whereas the membrane‐binding approach failed to detect these receptor subtypes with certainty. The present study indicates that previous estimates of alpha‐1 AR density and alpha‐1 AR subtypes obtained by a conventional membrane‐binding approach, as opposed to our improved tissue segment‐binding assay, may have substantially underestimated the abundance of receptors present in arterial tissues, and may have failed to identify accurately the presence of receptor subtypes. Advantages and disadvantages of the tissue segment‐binding approach are discussed.


Pharmacology | 2002

Binding and functional affinity of sarpogrelate, its metabolite M-1 and ketanserin for human recombinant alpha-1-adrenoceptor subtypes

Malika Israilova; Fumiko Suzuki; Takashi Tanaka; Takafumi Nagatomo; Takanobu Taniguchi; Ikunobu Muramatsu

Serotonin (5-HT2) antagonists show high affinity for the α1-adrenoceptor (α1-AR) in addition to the 5-HT2 receptor. In the present study we compared the pharmacological characteristics of a new 5-HT2 antagonist sarpogrelate and its active metabolite M-1 with those of ketanserin on human recombinant α1-AR subtypes. In the binding study, sarpogrelate, M-1 and ketanserin produced concentration-dependent inhibition of 3H-prazosin binding to α1-ARs. Among the three drugs, ketanserin showed the highest affinity for α1a-, α1b- and α1d-ARs (pKi 8.0, 8.3 and 7.6, respectively). Sarpogrelate had a relatively low affinity for the three subtypes (6.3 , 6.4 and 6.3, respectively) and M-1 showed medium affinity (7.1, 7.1 and 6.1, respectively). Chinese hamster ovary (CHO) cells expressing each α1-AR subtype showed concentration-dependent inositol phosphate (IP) accumulation in response to phenylephrine. The concentration response curves were shifted to the right by three drugs, and the pKb values were close to the pKi values in the binding study. In addition to these effects, sarpogrelate and M-1, but not ketanserin produced an increase in the basal IP level of α1d-expressed CHO cells, although the increase was less than that of phenylephrine. The present results indicate that sarpogrelate and M-1 have antagonistic activity to the three α1-AR subtypes, but their affinities are significantly lower than those of ketanserin.


Life Sciences | 1982

Trigeminal nerve: the possible origin of substance p-nergic response in isolated rabbit iris sphincter muscle.

Naoko Ueda; Ikunobu Muramatsu; Haruki Hayashi; Motohatsu Fujiwara

We determined the effects of trigeminal nerve denervation on the noncholinergic, nonadrenergic response to electrical transmural stimulation of the isolated rabbit iris sphincter muscle. The left ophthalmic nerve (first branch of the trigeminal nerve) was cut at the intracranial, peripheral site of the trigeminal ganglion and five to ten days later, the iris sphincter muscle isolated from the left eye (operated side) was found to produce a fast cholinergic contraction in response to electrical transmural stimulation and there was no evidence of noncholinergic, nonadrenergic contractions. On the other hand, in the iris sphincter muscle isolated from the right eye (control side), electrical transmural stimulation produced both cholinergic and noncholinergic, nonadrenergic contractile responses. Capsaicin and bradykinin produced noncholinergic, nonadrenergic contractile responses in the muscle from the control side, while in the iris sphincter from the trigeminally denervated eye there was no such response to application of these drugs. Exogenous substance P (SP) and carbachol produced a strong contractile response in both the trigeminally innervated and denervated sphincter muscles. Somatostatin, vasoactive intestinal polypeptide (VIP) and enkephalin were without effects. These observations suggest that the noncholinergic, nonadrenergic responses to electrical transmural stimulation are derived from the trigeminal nerve and that the mediator involved is probably SP or a related peptide.


Life Sciences | 2002

Augmentation of NO-mediated vasodilation in metabolic acidosis.

Kaoru Hattori; Shinya Tsuchida; Hirokazu Tsukahara; Mitsufumi Mayumi; Takashi Tanaka; Li Zhang; Takanobu Taniguchi; Ikunobu Muramatsu

Reduction of perivascular pH in acidemia produces hyporesponsiveness of vascular bed to vasoconstrictors. In the present study, we examined the effects of modest acidification on dilatory responses of isolated rat thoracic aorta. Acetylcholine produced endothelium-dependent relaxation in phenylephrine-precontracted aorta, which was markedly enhanced by acidification of Krebs-Henseleit solution from pH 7.4 to 7.0. A similar augmentation was observed in the relaxing responses to NO donors (SNP, SIN-1, SNAP), 8-Br-cGMP and NS-1619 (a putative K(Ca) channel opener and/or Ca channel inhibitor) in endothelium-denuded, phenylephrine-contracted aorta. However, papaverine-induced relaxation was not affected by the change in pH. At pH 7.4, the relaxing responses to acetylcholine and SNP were partially inhibited by charybdotoxin (K(Ca) channel inhibitor) but not glibenclamide (K(ATP) channel inhibitor), while at pH 7.0 the relaxation induced by either drug was not affected by K(+) channel inhibitors. Relaxation induced by 8-Br-cGMP or NS-1619 was not inhibited by charybdotoxin or glibenclamide. Acidification to pH 7.0 increased the cGMP production in response to acetylcholine in endothelium-intact aorta and to SNP in endothelium-denuded aorta. These results show that modest acidification augments NO-mediated relaxation in rat aorta, probably due to an enhancement of cGMP-dependent but K(+) channel-unrelated relaxation mechanisms.


British Journal of Pharmacology | 2002

Alpha-1 adrenoceptor up-regulation induced by prazosin but not KMD-3213 or reserpine in rats

Li Zhang; Takanobu Taniguchi; Takashi Tanaka; Kazumasa Shinozuka; Masaru Kunitomo; Masahiko Nishiyama; Koji Kamata; Ikunobu Muramatsu

We have investigated the effects of chronic administration of prazosin (a subtype‐nonspecific alpha‐1 AR antagonist), KMD‐3213 (an alpha‐1A AR subtype‐specific antagonist) and reserpine (a catecholamine depletor) on the density of alpha‐1 AR subtypes in various rat tissues (liver, kidney, submaxillary gland, heart and spleen). Administration of prazosin (2u2003mgu2003kg−1u2003day−1, i.p.) for 2 weeks did not affect KD values for [3H]‐prazosin or [3H]‐KMD‐3213 of alpha‐1 ARs in five rat tissues tested. However, it caused 52% up‐regulation of alpha‐1B AR in the spleen, and 84% and 107% up‐regulation of alpha‐1A‐ and alpha‐1B ARs, respectively, in the heart. Although major subtypes of alpha‐1 AR are alpha‐1A AR in the submaxillary gland, alpha‐1B AR in the liver, and alpha‐1A and alpha‐1B ARs in the kidney, these tissues showed no up‐regulation. The mRNA levels of alpha‐1 AR subtypes were not affected by prazosin administration in any tissue tested. Neither administration of KMD‐3213 (2u2003mgu2003kg−1u2003day−1, i.p.) nor reserpine (0.5u2003–u20031u2003mgu2003kg−1u2003day−1, i.p.) for 2 weeks caused any change in either the binding affinity for [3H]‐prazosin or [3H]‐KMD‐3213 or the density of the alpha‐1 AR subtypes in the five rat tissues. Neither prazosin nor KMD‐3213 treatment reduced the noradrenaline content in the five rat tissues, in contrast to reserpine treatment, which markedly reduced it. The findings of the present study demonstrated that up‐regulation of alpha‐1 AR is selectively caused by prazosin treatment in some tissues but neither by KMD‐3213 treatment nor by chemical denervation with reserpine. These results suggest that up‐regulation of alpha‐1 ARs is not caused by a simple blockade of sympathetic tone.


European Journal of Pharmacology | 1977

The effects of destruction on noradrenergic ascending ventral bundles and tetrabenazine on formation of stress-induced gastric ulcer

Yoshitsugo Osumi; Ikunobu Muramatsu; Motohatsu Fujiwara

The possibility that hypothalamic noradrenaline (NA) plays a role in the formation of gastric ulcers under stress via ventral bundles (VB) was examined in rats after bilateral destruction of VB. After a 3-h restraint stress ulcerative changes were observed in the stomach of sham-operated rats. NA contents in the hypothalamus and cerebral cortex decreased as compared to the respective contents before stress. The VB-lesioning inhibited the stress-induced decrease of NA in the hypothalamus. Ulcer indices in the animals 1 or 7 days after the VB-lesioning, however, did not differ from those of controls. Pretreatment of sham-operated controls with tetrabenazine enhanced the stress-induced decrease of NA in the brain, and exacerbated the gastric ulceration. VB-lesioning completely blocked these effects of tetrabenazine. It appears that the tetrabenazine-induced mobilization of hypothalamic NA via VB causes an aggravation of gastric ulceration.


British Journal of Pharmacology | 2004

Alpha-1D adrenoceptors are involved in reserpine-induced supersensitivity of rat tail artery

Naoyuki Taki; Takashi Tanaka; Li Zhang; Fumiko Suzuki; Malika Israilova; Takanobu Taniguchi; Yasuko Hiraizumi-Hiraoka; Kazumasa Shinozuka; Masaru Kunitomo; Ikunobu Muramatsu

We examined reserpine‐induced chemical denervation supersensitivity with special reference to alpha‐1 adrenoceptor (AR) subtypes. Chronic treatment with reserpine for 2 weeks depleted noradrenaline in the tail artery and spleen of rats. Noradrenaline in the thoracic aorta was negligible before and after reserpine treatment. The treatment with reserpine produced supersensitivity in the contractile responses of the rat tail artery to phenylephrine, 5‐HT and KCl, resulting in leftward shift of concentration–response curves (11.6‐, 2.5‐ and 1.1‐fold at EC50 value, respectively). These results suggest a predominant sensitization of the alpha‐1 AR‐mediated response by reserpine treatment. BMY 7378 at a concentration (30 nM) specific for blocking the alpha‐1D AR subtype, but not KMD‐3213 at a concentration (10 nM) selective for blocking the alpha‐1A AR subtype, inhibited the supersensitivity of the phenylephrine‐induced response in the reserpine‐treated artery. On the other hand, the response to phenylephrine in reserpine‐untreated artery was selectively inhibited by the same concentration of KMD‐3213, but not by BMY 7378. Prazosin, a subtype‐nonselective antagonist, blocked the responses to phenylephrine with the same potency, regardless of reserpine treatment. In the thoracic aorta and spleen, no supersensitivity was produced in the responses to phenylephrine by reserpine treatment. In a tissue segment‐binding study using [3H]‐prazosin, the total density and affinity of alpha‐1 ARs in the rat tail artery were not changed by treatment with reserpine. However, alpha‐1D AR with high affinity for BMY 7378 was significantly detected in reserpine‐treated tail artery, in contrast to untreated artery. Decreases in alpha‐1A AR with high affinity for KMD‐3213 and alpha‐1B AR with low affinities for KMD‐3213 and BMY 7378 were also estimated in reserpine‐treated tail artery. Alpha‐1D AR mRNA in rat tail artery increased to three‐folds by reserpine treatment, whereas the levels of alpha‐1A and 1B mRNAs were not significantly changed. The present results suggest that chronic treatment with reserpine affects the expression of alpha‐1 AR subtypes of rat tail artery and that the induction of alpha‐1D ARs with high affinity for catecholamines is in part associated with reserpine‐induced supersensitivity.

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Kazumasa Shinozuka

Mukogawa Women's University

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Masaru Kunitomo

Mukogawa Women's University

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