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Volume 63 (1993)
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Volume 63, Issue 2
Displaying 1-19 of 19 articles from this issue
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Tomihisa Kawasaki, Susumu Kawamura, Satomi Katoh, Toichi Takenaka1993 Volume 63 Issue 2 Pages 135-142
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe compared the thrombolytic activity of a novel modified t-PA, YM866, with that of t-PA in a rat model of electrically-induced thrombosis. Histological examination revealed the thrombus to be composed mainly of platelet clumps. Measurement of the decrease in carotid blood flow showed that complete occlusion occurred within 14 min. At 10 min after the induction of thrombus, a test drug (YM866, t-PA, or saline) was administered by i.v. bolus injection under heparinization (300 IU/kg, i.v.). Both YM866 and t-PA exhibited dose-dependent thrombolytic activity; the reperfusion rate of YM866 was twice that of t-PA. There was no significant difference in time to reperfusion between the agents, but YM866 showed a greater improvement in patency status after successful thrombolysis than t-PA. Plasma fibrinogen fell slightly but significantly (14% of baseline value) in animals given 1 mg/kg of YM866. All groups of rats showed a significant decrease in carotid artery blood flow at 1 hr after successful reperfusion or injection of the drug, but this decrease showed significant recovery in animals given 1 mg/kg of YM866. These results suggest that YM866 by single bolus injection is a superior thrombolytic agent to t-PA, and that YM866 can improve the patency status after successful thrombolysis. Furthermore, this platelet-rich thrombosis model permits continuous observation of the process of thrombus formation and subsequent thrombolysis and provides a useful tool for the screening and evaluation of efficacy of new antithrombotic agents.View full abstractDownload PDF (777K) -
Junkichi Izumi, Masahiro Inagaki, Yuji Kiuchi, Manabu Matsumoto, Yukak ...1993 Volume 63 Issue 2 Pages 143-149
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe investigated the changes in striatal monoaminergic functions, focusing on the release and metabolism, in a cerebral ischemic model induced by a 5-min bilateral occlusion of the carotid arteries (BOCA) and reperfusion in anesthetized gerbils. In the microdialysis study, the striatal extracellular level of dopamine (DA) markedly increased (144-fold) immediately after BOCA. Although norepinephrine (NE) and 5-hydroxytryptamine (5-HT) could not be detected in the dialysates throughout the baseline period, they increased to detectable levels after BOCA. On the contrary, the tissue contents of NE and 5-HT decreased or tended to decrease up to 4 hr following reperfusion. Striatal DA contents did not show any changes in the early period after ischemia-reperfusion and slightly increased at 4 hr or later. Tissue contents of 3-methoxytyramine (3-MT), a metabolite of DA by catechol-O-methyltransferase (COMT), increased 0 and 5 min after reperfusion. Normethanephrine (NMN), which is a metabolite of NE by COMT, also increased not only 5 min after but also up to 4 hr after ischemia-reperfusion, indicating a sustained increase in NE release. These results suggested that the neuronal activity of NE, which is supposed to exert a protective effect on ischemic damage, was enhanced for a longer period than that of DA after transient ischemia.View full abstractDownload PDF (550K) -
Ken-ichiro Hoshiko, John Morley1993 Volume 63 Issue 2 Pages 151-157
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSIn passively sensitized guinea pigs, slow infusion of an amount of ovalbumin insufficient to evoke airway obstruction induces hyperreactivity of the airways. A wide range of changed responsivity was observed for different test spasmogens, with leukotriene C4 > histamine > prostaglandin F2α > bradykinin > leukotriene E4 > serotonin > acetylcholine. Injection of ovalbumin as a bolus produced pronounced airway obstruction without hyperreactivity. Airway obstruction due to vascular engorgement (dextran infusion) or edema (histamine infusion) did not result in hyperreactivity. Infusion of PAF induced pronounced airway obstruction together with hyperreactivity, but with a rank order of histamine > leukotriene C4 > serotonin > bradykinin > leukotriene E4 > acetylcholine. It can be concluded that allergic airway hyperreactivity in the guinea pig is spasmogen-selective and largely independent of airway obstruction. These observations question the presumption of non-selective hyperreactivity in allergic asthma and cast doubt upon the proposal that airway hyperreactivity is secondary to airway obstruction.View full abstractDownload PDF (509K) -
Ken-ichiro Hoshiko, John Morley1993 Volume 63 Issue 2 Pages 159-163
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSIn guinea pigs passively sensitized to ovalbumin, sustained (6 days) subcutaneous infusion of (±)salbutamol (1 mg/kg/day) induced significant airway obstruction and heightened responsivity to airway spasmogens. Of these animals, a substantial proportion (78/235) were too responsive to injected spasmogens to permit infusion of ovalbumin or died following infusion of ovalbumin; yet there were few deaths (2/166) amongst the sensitized animals not exposed to (±)salbutamol. In comparison to the animals not exposed to (±)salbutamol, infusion of ovalbumin led to exaggerated responsivity of the airways to leukotriene C4, leukotriene E4, histamine, serotonin and acetylcholine, but not to prostaglandin F2α or bradykinin. The capacity of sustained exposure to high doses of (±)salbutamol to induce airway hyperreactivity to allergic mediators may account for an association between asthma death and regular, excessive use of sympathomimetics.View full abstractDownload PDF (385K) -
Ying-Li Qu, Kentaro Sugiyama, Takafumi Nagatomo, Takashi Maniwa, Akira ...1993 Volume 63 Issue 2 Pages 165-169
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe interaction of SM-6586 (methyl 1, 4-dihydro-2, 6-dimethyl-3-{3-(N-benzyl-N-methyl-aminomethyl)-1, 2, 4-oxadiazolyl-5-yl}-4-(3-nitrophenyl)pyridine-5-carboxylate) with the specific binding of 3H-PN200-110 to rat heart and brain membranes was characterized and compared with those of other Ca2+ antagonists. The blockade of 3H-PN200-110 binding sites induced by nifedipine, nitrendipine and nimodipine was reversed by washing, whereas the blockade by SM-6586 was not readily reversed under these conditions. No significant difference was found in irreversibility between SM-6586 enantiomers. When rat aortic strips were pretreated with SM-6586, the contractions induced by 50 mM KCl were inhibited even though SM-6586 was not present in the extracellular medium. This residual inhibitory effect was much stronger than that of nicardipine. The inhibition of KCl-induced contractions by nifedipine and nitrendipine was easily reversed by washing. Thus, we suggest that (+)SM-6586 is a novel 1, 4-dihydropyridine derivative having a very slow rate of dissociation from the binding site. This property may explain its long-lasting antihypertensive effect.View full abstractDownload PDF (305K) -
Kyouko Fukami, Mitsue Itagaki, Seiichi Komori, Hidenori Ohashi1993 Volume 63 Issue 2 Pages 171-179
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSTo characterize the calcium (Ca2+)-releasing effects of histamine and GTPγS, the drug-induced tension developments were measured in β-escin-treated skinned longitudinal smooth muscle of guinea pig ileum. Intracelluar Ca2+ stores were loaded with Ca2+ by incubating the muscle for 10 min in a Ca2+-containing solution. Histamine (10-100 μM), applied after Ca2+-loading, produced a transient rise in tension. The effect of histamine was not preserved after treatment with 20 mM caffeine, a Ca2+-store releaser. The effect of histamine was potentiated by GTP; inhibited by GDPβS, an antagonist of GTP for binding to G-proteins; or heparin, an antagonist of inositol 1, 4, 5-trisphosphate (IP3) for binding to its receptor; and mimicked by IP3. When GTPγS (20 μM) was applied and continued to be present for 15 min, a transient rise in tension followed by a small, sustained rise in tension was elicited. The effect of GTPγS was completely inhibited by GDPβS. The initial, transient component of the biphasic GTPγS response was abolished or markedly inhibited after treatment with caffeine, heparin or the calcium ionophore A23187. The present results suggest that histamine and GTPγS cause a release of Ca2+ from caffeine-sensitive stores which is mediated by IP3 formed through a G-protein-coupled mechanism. The GTPγS-induced Ca2+ release is not considered to involve such an IP3-independent process as described in chemically-skinned arterial muscle.View full abstractDownload PDF (584K) -
Hiromi Tsushima, Mayumi Mori, Tomohiro Matsuda1993 Volume 63 Issue 2 Pages 181-186
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe effects of D-Ala2-D-Leu5-enkephalin (DADL, a δ-opioid agonist), microinjected directly into the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, on urine outflow rate, urinary osmotic pressure, blood pressure, heart rate, respiratory rate and rectal temperature were investigated in water-loaded and ethanol-anesthetized rats. The microinjection of DADL into both the nuclei decreased urine outflow rate in a dose-dependent manner with an increase in urinary osmotic pressure, but did not change the other recorded parameters. The DADL-induced antidiuretic effect in the SON was inhibited by naloxone, but not by atropine, phenoxybenzamine, timolol nor a vasopressin antagonist, d(CH2)5-D-Tyr(Et)VAVP. The effect in the PVN was inhibited by naloxone, atropine, timolol and d(CH2)5-D-Tyr(Et)VAVP, but not by phenoxybenzamine. These results suggest that DADL causes antidiuretic effects mediated through opioid receptors in both the SON and PVN, and the underlying mechanisms are different between them. Involvement of δ-opioid receptors in the DADL-induced antidiureses was discussed.View full abstractDownload PDF (428K) -
Akihiro Matsuura, Hiroshi Okumura, Rieko Asakura, Naoki Ashizawa, Mayu ...1993 Volume 63 Issue 2 Pages 187-193
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSAspergillomarasmine-A and -B (AM-A and -B), which were isolated from the cultured broth of an unidentified fungus N877, showed apparent inhibition against endothelin-converting enzyme (ECE) from bovine endothelial cells as measured by the formation of endothelin-1 (ET-1) converted from big endothelin-1 (bET-1), with IC50 values of 3.4 and 2.5 μM for AM-A and -B, respectively. EDTA also inhibited ECE (IC50=1.1 μM), but the inhibitions by AM-A, AM-B and EDTA were each abolished by the addition of 10 μM Zn2+ to the reaction mixture. In mice, AM-A and -B dose-dependently (10-50 mg/kg, i.v.) caused significant prolongation of the latency to sudden death induced by i.v. bET-1 (25 nmol/kg), but not that by ET-1 (5 nmol/kg), accompanied by a decrease in plasma immunoreactive ET-1 formation, while EDTA (24 mg/kg) failed to do so. In mice, the LD50 value of AM-A was calculated to be 159.8 mg/kg, i.v., which was much larger than that of EDTA (28.5 mg/kg, i.v.), indicating the low toxicity of AM-A. AM-A (30 mg/kg, i.v.) also suppressed bET-1-induced hemoconcentration and hypertension in mice and rats, respectively. These findings suggest that although ECE inhibition by AM-A was mainly attributable to its chelating activity, it showed apparent in vivo activities due to ECE inhibition with low toxicity.View full abstractDownload PDF (508K) -
Kazuhiro Ohmi, Shigeru Yamashita, Yoshiaki Hashimoto, Yoshiaki Nonomur ...1993 Volume 63 Issue 2 Pages 195-202
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSK-252a, a protein kinase inhibitor with a wide spectrum of activity, inhibited the serumstimulated proliferation of cultured bovine carotid endothelial cells dose-dependently, and all the cells became remarkably large, with a diameter of more than 150 pm at K-252a concentrations of 0.3 -1 μg/ml. This effect of the agent was reproducible under the conditions described in this article. When the endothelial cells became abnormally large by K-252a, the surface area of the cell became wider, and the F-actin molecules increased in both number and length. Despite their abnormal size, K-252a-induced giant cells maintained at least three physiological functions characteristic to normal endothelial cells: 1) ability to take up acetylated low density lipoprotein, 2) ability to produce and secrete endothelin and 3) ability to respond via an increase of [Ca2+]i to the stimulation by bradykinin. These observations suggest that K-252a-induced giant cells are useful tools for examining the function of endothelial cells because it is very reproducible and can be produced by an easy treatment.View full abstractDownload PDF (986K) -
Masayoshi Yamaguchi, Seiko Kishi1993 Volume 63 Issue 2 Pages 203-207
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe effect of β-alanyl-L-histidinato zinc (AHZ), in which zinc is chelated to β-alanyl-L-histidine, on bone metabolism was investigated in the femoral diaphysis of ovariectomized rats. AHZ (10, 30 and 100 mg/kg body weight/day) was orally administered to ovariectomized rats for 3 months. Ovariec tomy significantly decreased the estradiol concentration in the serum as compared with that from sham-operated rats. This decrease was not altered by the dose of AHZ. The bone volume and dry weight in the femur of ovariectomized rats significantly decreased in comparison with those from sham-operated rats. Moreover, alkaline phosphatase activity, deoxyribonucleic acid (DNA) and calcium contents in the femoral diaphysis were significantly decreased by ovariectomy. The decreases of the femoral volume and dry weight, the femoral-diaphyseal alkaline phosphatase activity, DNA and calcium contents by ovariectomy were completely prevented by the tested doses of AHZ (10, 30 and 100 mg/kg/day). AHZ in the dose range of 10 100 mg/kg/day caused a significant increase in zinc content in the femoral diaphysis of ovariectomized rats. The present study suggests that the prolonged administration of AHZ can prevent bone loss by ovariectomy.View full abstractDownload PDF (360K) -
Nobuhiro Inatomi, Takashi Satoh, Hiroshi Satoh, Zen Itoh, Satoshi Omur ...1993 Volume 63 Issue 2 Pages 209-217
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe effect of EM523 [de(N-methyl)-N-ethyl-8, 9-anhydroerythromycin A 6, 9-hemiacetal], an erythromycin derivative, on gastrointestinal motility was investigated using conscious dogs in the fasting state, and it was compared with those of motilin and prostaglandin F2α (PGF2α). EM523 and motilin given as i.v. infusions induced strong contractions in the stomach that migrated along the intestine. On the other hand, PGF2α stimulated intestinal contractions, but its effect on gastric motility was weak. EM523 had 1/50 the potency of motilin and 6 times the potency of PGF2α for stimulation of intestinal motility. Atropine at 0.1 mg/kg, i.v. strongly inhibited gastrointestinal contractions induced by EM523 or motilin and partly inhibited PGF2α-induced intestinal motility. ICS-205-930, a 5HT3-receptor antagonist, at a dose of 1 mg/kg, i.v. strongly inhibited EM523 or motilin-induced gastric contractions but did not affect the action of PGF2α. Infusion of EM523 at 100 μg/kg/hr induced strong migrating contractions even when motility was depressed by dopamine infusion or laparotomy. Infusion of PGF2α at 300 μg/kg/hr stimulated intestinal but not gastric motility under these conditions. The results of this study indicate that the cholinergic pathway and 5HT3 receptors are involved in EM523 and motilin-induced migrating gastrointestinal contractions, whereas the cholinergic pathway seems to be only partly involved in PGF2α-induced intestinal contractions.View full abstractDownload PDF (536K) -
Yoshinobu Yamazaki, Masuo Akahane, Mamoru Kobayashi, Makio Kitazawa, Y ...1993 Volume 63 Issue 2 Pages 219-225
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSPharmacological effects of KSG-504, a newly synthesized compound, on the response induced by exogenous CCK-8 were investigated. KSG-504 inhibited 125I-CCK-8 binding to both rat pancreas and cerebral cortex with IC50 values of 2.0×10-7 M and 8.0×10-5 M, respectively. The selectivity ratio of KSG-504 for pancreatic CCK receptor (CCK-A) was estimated as 400. In the isolated pancreatic acini of rats, KSG-504 caused a parallel rightward shift of the concentration-response curve for CCK-8-stimulated amylase release with no change in its maximal response, indicating a competitive antagonism of the drug for the CCK-A receptor (Schild plot analysis; slope=0.927, pA2=6.9). In addition, KSG-504 produced a significant inhibition of CCK-8-induced pancreatic amylase secretion when administered intravenously or intraduodenally to rats (ED50: 52 μg/kg/min by the i.v. route and 12.1 mg/kg by the i.d. route). KSG-504 had equipotent inhibitory effects on both CCK-8-stimulated pancreatic secretion and gallbladder contraction in dogs with ED50 values of 0.98 and 0.84 mg/kg, respectively. KSG-504 also inhibited the CCK-8-induced contraction of isolated guinea pig ileum in a concentration-dependent manner (IC50=3.0×10-6 M). These results demonstrate that KSG-504 is a competitive and selective CCK-A-receptor antagonist that is effective in vivo after oral administration.View full abstractDownload PDF (513K) -
Junichi Kurihara, Satoru Tamaoki, Hitoshi Kato1993 Volume 63 Issue 2 Pages 227-233
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSThe influence of 5-min global cerebral ischemia on the facilitatory modulation of the vagal baroreflex through central α2-adrenoceptors or by the electrical stimulation of the septum was investigated in anesthetized dogs. Reflex bradycardia was produced by a bolus injection of phenylephrine at a dose which produces about a 25-mmHg increase in mean blood pressure. The ischemia was produced by the occlusion of the brachiocephalic and the left subclavian arteries with preceding ligation of the intercostal arteries. Clonidine at 10 μg, administered intracisternally, decreased the blood pressure and heart rate and facilitated the vagal reflex bradycardia. During the reperfusion period following ischemia, however, clonidine failed to affect the reflex bradycardia. Electrical stimulation of the septal region facilitated the reflex bradycardia without marked influences on the basal blood pressure and heart rate. The facilitatory effect was dependent on the frequency (10 to 75 Hz) and amplitude (3 to 15 V) of stimulation and was not observed after vagotomy or ischemic insult. These results suggest that 5-min global cerebral ischemia may produce the dysfunction of the neurons which are closely related to the baroreflex loop and receive the facilitatory modulation through α2-adrenoceptors and/or from the forebrain structures, leading to the dysfunction of the vagal baroreflex.View full abstractDownload PDF (464K) -
Yoshiyuki Miyamoto, Naonori Morita, Nobuo Nakamura, Tetsuji Yamanishi, ...1993 Volume 63 Issue 2 Pages 235-240
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe investigated whether the distribution (concentration) of morphine in the central nervous system (CNS) after systemic administration could be an index for the in vivo binding of morphine. Neither the morphine concentration nor its decline correlated with the density of opiate receptors. Naloxone decreased the morphine concentration in some CNS regions and plasma after a high dose of morphine, but not after a small dose of morphine. The CNS regions in which naloxone decreased the morphine concentration did not correlate with the density of opiate receptors, and the concentration ratios (CNS regions versus plasma) of morphine were not affected by naloxone. These results suggested that the morphine concentration in the CNS did not reflect the in vivo binding of morphine and that the naloxone-induced decrease in morphine concentration was not due to a displacement of morphine from its receptor sites but due to a change in morphine kinetics. Pharmacokinetic studies suggested that naloxone decreased the morphine concentration through an increased volume of morphine distribution. This naloxone-induced decrease in morphine concentration may contribute to the naloxone-induced inhibition of morphine action in addition to the competitive antagonism at opiate receptors.View full abstractDownload PDF (438K) -
Tomoaki Shinkawa, Yutaka Kato, Naoko Tsuchiya, Fumiaki Yamasaki, Akio ...1993 Volume 63 Issue 2 Pages 241-249
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe investigated the effects of a novel diuretic, M17055, on blood pressure and cardiovascular hypertrophy in spontaneously hypertensive rats (SHR). M17055 was orally administered once a day for 24 consecutive days to 14-week-old male SHR. M17055 at doses of 1.25, 2.5 and 5 mg/kg/day exerted a dose-related diuretic and antihypertensive effect during the treatment. The weight of the left ventricle normalized by body weight on the following day of the last dosage was significantly (P<0.01) reduced by M17055 at doses of 2.5 and 5 mg/kg/day in a dose-dependent manner. The effect of M17055 on cardiac hypertrophy was more potent (P<0.01) than that of captopril, when the comparison was performed at the doses of M17055 and captopril inducing the same extent of blood-pressure decrement. Vascular hypertrophy was evaluated by the media/lumen ratio (M/L) in the thoracic aorta and the first branch of the superior mesenteric artery. In the aorta, M/L was slightly, but not significantly, decreased by M17055 at doses of 2.5 and 5 mg/kg/day, whereas it was decreased significantly (P<0.01) by captopril. In the mesenteric artery, the ratio was significantly (P<0.05) reduced by M17055 at a dose of 5 mg/kg/day. These results suggest that M17055 possesses beneficial properties for the clinical treatment of hypertension.View full abstractDownload PDF (624K) -
Yoshifumi Hatakeyama, Masahiko Matsuo, Masaaki Tomoi, Jo Mori, Masanob ...1993 Volume 63 Issue 2 Pages 251-256
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe investigated the participation of prostaglandins (PG) and nitric oxide (NO) in adaptive cytoprotection using 0.6 N HCl-induced gastric lesions in the rat stomach. Indomethacin reversed the protective effect of 0.2 N HCl more strongly than that of 0.35 N HCl, both of which markedly inhibited HCl ulcer. NG-Nitro-L-arginine (L-NNA) did not affect the protective effect afforded by either 0.2 N HCl or 0.35 N HCl. Combined pretreatment with indomethacin and L-NNA did not diminish the protective action induced by 0.35 N HCl, but almost completely abolished the indomethacin-resistant protection afforded by 0.1 N NaOH. Acid mild irritant increased the gastric fluid volume concentration-dependently, whereas alkaline mild irritant had little or no effect on the volume. These results suggest that: 1) The mediators involved in adaptive cytoprotection afforded by 0.1 N NaOH may be fully ascribed to PG and NO; 2) PG is a major mediator in the protection induced by 0.2 N HCl; 3) In the case of 0.35 N HCl, the mediators remain to be determined since increased gastric fluid volume could contribute to the protection through dilution. These findings thus may indicate that multiple mediators and mechanisms are implicated in adaptive cytoprotection.View full abstractDownload PDF (441K) -
Hideaki Mizumoto, Akira Karasawa1993 Volume 63 Issue 2 Pages 257-259
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSEffects of an adenosine A1-receptor agonist and antagonist were determined in pertussis toxin (IAP)-treated and non-treated rats. (-)-N6-(2-phenylisopropyl) adenosine, an adenosine A1-agonist, reduced the urine volume and sodium excretion without decreasing the glomerular filtration rate at 0.1 mg/kg (p.o.) in both IAP-treated and non-treated rats. Diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1, 3-dipropylxanthine) and 8-cyclopentyl-1, 3-dipropylxanthine, adenosine A1-receptor antagonists, were not affected by pretreatment with IAP. These results suggest that endogenous adenosine may induce antidiuretic effects by accelerating the reabsorption of water and sodium at tubular sites via an IAP-insensitive mechanism, and that the diuretic effects of the adenosine A1-receptor antagonist may result from inhibiting this action of endogenous adenosine.View full abstractDownload PDF (191K) -
Ryozo Oishi, Yoshinori Itoh, Naoto Adachi, Kiyomi Saeki1993 Volume 63 Issue 2 Pages 261-264
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSEffect of MCI-225 on brain monoamine metabolism was examined in rats. MCI-225 (30 mg/kg, p.o.) had no influence on noradrenaline (NA) levels, but significantly inhibited the NA turnover in the hippocampus and hypothalamus. This compound also significantly increased the 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine ratio in the cerebral cortex, hippocampus and striatum; and it enhanced the probenecid-induced 5-HIAA accumulation in the striatum. In the microdialysis study, MCI-225 markedly increased the NA output, but decreased the 3, 4-dihydroxyphenylethyleneglycol output from the hypothalamus of urethane-anesthetized rats. These results suggest that MCI-225 enhances both noradrenergic and serotonergic function by inhibiting NA uptake and accelerating 5-HT turnover, respectively.View full abstractDownload PDF (214K) -
Tatsuya Mori, Takahiro Moriyama, Akira Karasawa1993 Volume 63 Issue 2 Pages 265-268
Published: 1993
Released on J-STAGE: April 12, 2006
JOURNAL FREE ACCESSWe investigated the effects of KW-3902 (8-(noradamantan-3-yl)-1, 3-dipropylxanthine), a newly-synthesized selective adenosine A1-receptor antagonist, on the shortening of action potential duration (APD) in guinea pig atria exposed to adenosine. The APD shortening by adenosine was inhibited by KW-3902 at higher than 10-8 M, but not by 10-5 M of KF17837, an adenosine A2-receptor antagonist. These results support the notion that the APD shortening by adenosine in atria is mediated via adenosine A1-receptors. The potency of KW-3902 in antagonizing the APD-shortening were similar to those in antagonizing the negative inotropic and chronotropic action of adenosine in the isolated right atria, suggesting that these responses to adenosine are mediated via the receptors of the same type.View full abstractDownload PDF (257K)
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