巻号一覧
89 巻 (2002)
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89 巻, 3 号
選択された号の論文の21件中1～21を表示しています
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Forum Minireviews
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PrefaceMinoru Narita, Shinobu Sakurada専門分野: Infomation Science
2002 年 89 巻 3 号 p. 201-202
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーPDF形式でダウンロード (73K) -
Isolation and Distribution of Endomorphins in the Central Nervous SystemJames E. Zadina専門分野: Infomation Science
2002 年 89 巻 3 号 p. 203-208
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーEndomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2) have the highest affinity and selectivity for the μ-opioid receptor (MOP-R) of all known mammalian opioids. They were isolated from bovine and human brain, and are structurally distinct from the other endogenous opioids. Both EM-1 and EM-2 have potent antinociceptive activity in a variety of animal models of acute, neuropathic and allodynic pain. They regulate cellular signaling processes in a manner consistent with MOP-R-mediated effects. The EMs are implicated in the natural modulation of pain by extensive data localizing EM-like immunoreactivity (EM-LI) near MOP-Rs in several regions of the nervous system known to regulate pain. These include the primary afferents and their terminals in the spinal cord dorsal horn, where EM-2 is well-positioned to modulate pain in its earliest stages of perception. In a nerve-injury model of chronic pain, a loss of spinal EM2-LI occurs concomitant with the onset of chronic pain. The distribution of the EMs in other areas of the nervous system is consistent with a role in the modulation of diverse functions, including autonomic, neuroendocrine and reward functions as well as modulation of responses to pain and stress. Unlike several other μ opioids, the threshold dose of EM-1 for analgesia is well below that for respiratory depression. In addition, rewarding effects of EM-1 can be separated from analgesic effects. These results indicate a favorable therapeutic profile of EM-1 relative to other μ opioids. Thus, the pharmacology and distribution of EMs provide new avenues both for therapeutic development and for understanding the neurobiology of opioids.抄録全体を表示PDF形式でダウンロード (94K) -
Morphological Studies of the Endomorphinergic Neurons in the Central Nervous SystemQing-Ping Wang, James E. Zadina, Jian-Lian Guan, Seiji Shioda専門分野: Infomation Science
2002 年 89 巻 3 号 p. 209-215
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーEndomorphins (EMs) are newly found endogenous opioid peptides. Both endomorphin-1 (EM-1) and -2 (EM-2) are composed of four amino acids. Their high affinity and specificity for μ-opioid receptors have been confirmed by many physiological and pharmacological studies. In the present minireview, we discuss the distribution and localization of these peptides. While EM-2 is more prevalent in the spinal cord and lower brainstem, EM-1 is more widely and densely distributed throughout the brain than EM-2. We also discuss the possible coexistence of EM with other neurotransmitters. Finally, we introduce some new results regarding the ultrastructure and synaptic relationships of EM-2 obtained by the immunoelectron microscopic method.抄録全体を表示PDF形式でダウンロード (1331K) -
The Antinociceptive Properties of Endomorphin-1 and Endomorphin-2 in the MouseLeon F. Tseng専門分野: Infomation Science
2002 年 89 巻 3 号 p. 216-220
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーTwo highly selective μ-opioid receptor agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), have been identified and postulated to be endogenous μ-opioid receptor ligands. The present minireview describes the antinociceptive properties with the tail-flick test of these two ligands given intracerebroventricularly (i.c.v.) and intrathecally (i.t.) in ICR mice. EM-1 or EM-2 given i.c.v. or i.t. dose-dependently produce antinociception. These antinociceptive effects induced by EM-1 and EM-2 given i.c.v. or i.t. are selectively mediated by the stimulation of μ-, but not δ- or κ-opioid receptors. Like other μ-opioid agonists morphine and DAMGO ([D -Ala2,NMePhe4,Gly5-ol]enkephalin), EM-1 and EM-2 given i.c.v. activate descending pain controls by the releases of noradrenaline and 5-HT and subsequently act on α2-adrenoceptors and 5-HT receptors, respectively, in the spinal cord to produce antinociception. However, the antinociception induced by EM-2 given i.c.v. or i.t. also contain an additional component, which is mediated by the release of dynorphin A(1 – 17) acting on κ-opioid receptors at the supraspinal and spinal sites. In addition, the antinociception induced by EM-2 given i.c.v. contains another component, which is mediated by the release of Met-enkephalin acting on δ2-opioid receptors in the spinal cord. It is proposed that there are two subtypes of μ-opioid receptors,which are involved in EM-1- and EM-2-induced antinociception. One subtype of μ-opioid receptors is stimulated by EM-1, EM-2 and other μ-opioid agonists morphine and DAMGO; and another subtype of μ-opioid is sorely stimulated by EM-2 and is involved in the releases of dynorphin A(1 – 17) and Met-enkephalin for the production of antinociception.抄録全体を表示PDF形式でダウンロード (141K) -
Differential Antinociceptive Effects Induced by Intrathecally-Administered Endomorphin-1 and Endomorphin-2 in MiceShinobu Sakurada, Takafumi Hayashi, Masayuki Yuhki専門分野: Infomation Science
2002 年 89 巻 3 号 p. 221-223
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーTwo highly selective μ-opioid receptor (MOP-R) agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), have been identified and postulated to be endogenous ligands for MOP-R. Experiments were designed to determine the involvement of subtypes of MOP-R on the antinociceptive effects of EM-1 or EM-2 using the paw withdrawal test. The intrathecal (i.t.) injection of EM-1 and EM-2 produced dose-dependent antinociception in mice 1 min after the injection. Subcutaneous (s.c.) pretreatment with naloxonazine (NLZ), a selective MOP1-R antagonist, dose-dependently antagonized the antinociceptive effect of EMs. The antinociceptive effect of EM-2 was more sensitive to NLZ than that of EM-1. The selective heroin/morphine-6β-glucuronide antagonist 3-methoxynaltrexone (3-MNT) blocked EM-2-induced antinociception, but not EM-1-induced antinociception. The dose-response curve of EM-2 was shifted threefold to the right by pretreatment with s.c. 3-MNT at a dosage of 0.25 mg/kg. EM-2-induced antinociception was attenuated by pretreatment with s.c. nor-binaltorphimine and naltrindole, whereas the effect of EM-1 was not affected. Moreover, the antinociceptive effect of EM-2 was attenuated by i.t. pretreatment with antisera against dynorphin A(1 – 17) or methionine-enkephalin. These results suggest that EM-2-induced antinociception may be mediated by the subtype of MOP-R, which is sensitive to NLZ and 3-MNT, and by subsequent release of dynorphin A(1 – 17) and methionine-enkephalin in the spinal cord.抄録全体を表示PDF形式でダウンロード (97K) -
Endomorphin-Induced Motivational Effect: Differential Mechanism of Endomorphin-1 and Endomorphin-2Minoru Narita, Satoru Ozaki, Tsutomu Suzuki専門分野: Infomation Science
2002 年 89 巻 3 号 p. 224-228
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーThe newly discovered endogenous μ-opioid receptor (MOP-R) ligands endomorphin-1 (EM-1) and -2 (EM-2) exhibit the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. This review focuses on differential mechanism of the motivational effects induced by EM-1 and EM-2. In the [35S]GTPγS binding assay, either EM-1 or EM-2 causes a concentration-dependent G-protein activation in brain membrane of normal mice, whereas neither EM-1 nor EM-2 produces any activation of G-protein in membranes obtained from the MOP-R knockout mice. These results provide direct evidence at the molecular level that both EMs act on the MOP-R as the endogenous MOP-R agonists. Based on the conditioned place preference paradigm in mice, EM-1 given intracerebroventriculally produced a dose-related place preference. This effect was abolished by pretreatment with the MOP-R antagonist β-funaltrexamine (FNA) but not the δ-opioid receptor (DOP-R) antagonist naltrindole and the κ-opioid receptor (KOP-R) antagonist nor-bialtorphimine (BNI). Unlike EM-1, EM-2 exhibited a place aversion. The aversive effect was inhibited by not only β-FNA but also nor-BNI. Place aversion produced by EM-2 was also attenuated by pretreatment with an antiserum against an endogenous KOP-R ligand dynorphin A(1 – 17). These findings indicate that EM-1 may produce its rewarding effect via MOP-Rs. Furthermore, the aversive effect induced by EM-2 may be associated with the stimulation of the EM-1-insensitive MOP-R subtype and necessarily activate an endogenous KOPergic system in the mouse brain.抄録全体を表示PDF形式でダウンロード (287K) -
Differential Mechanism of G-Protein Activation Induced by Endogenous μ-Opioid Peptides, Endomorphin and β-EndorphinHirokazu Mizoguchi, Leon F. Tseng, Tsutomu Suzuki, Ichiro Sora, Minoru ...専門分野: Infomation Science
2002 年 89 巻 3 号 p. 229-234
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーIt is well documented that the μ-opioid receptor (MOP-R) is expressed by neurons in several central nervous system regions. Its occupancy with agonist drugs modulate a variety of physiological processes including pain, reward, stress, immune responses, neuroendocrine functions, and cardiovascular control. Based on the receptor binding assay, endomorphin-1 and endomorphin-2 have the highest specificity and affinity for the MOP-R of any endogenous substance so far described in the mammalian nervous system. In contrast, β-endorphin exhibits the strongest actions among endogenous opioid peptides mainly through the MOP-R; however, it also shows the distinct pharmacological actions. Recent cloning and expression studies have indicated that MOP-Rs are seven-transmembrane domain receptors whose actions are mediated through activation of heterotrimeric guanine nucleotide binding proteins (G-proteins). The activation of G-proteins by MOP-Rs can be measured by assessing agonist-induced stimulation of membrane binding of guanosine-5'-o-(3-[35S]thio)triphosphate ([35S]GTPγS). The subject of the present review is to focus on the differential mechanism underlying G-protein activation induced by these μ-opioid peptides using the [35S]GTPγS binding assay.抄録全体を表示PDF形式でダウンロード (193K)
Full Papers
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Yukio Ozaki, Kazushi Kunimatsu, Yoshitaka Hara, Ihachi Kato, Yosuke Ao ...専門分野: Infomation Science
2002 年 89 巻 3 号 p. 235-241
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーTo investigate the relationship between histological changes and distributions of medullasin, a neutrophil elastase-like serine proteinase, in phenytoin-induced gingival overgrowth, we established a rat model of gingival overgrowth. Thirty-two, 20-day-old male Fischer 344 rats were fed a diet containing phenytoin and sacrificed at 1, 2, 4 and 8 weeks. Control rats (n = 40) were fed the same diet, but without the drug and killed at the same weeks as experimental rats (n = 32) and 0 week (n = 8). The mandible specimens were resected and sectioned bucco-lingually between the first and second molars. A marked inflammatory-cell infiltration and elongated rete pegs were seen in the phenytoin-treated group. The extent of the overgrowth assessed by computer image analysis and the density of medullasin-positive cells by immunohistochemistry in the approximal gingiva showed a significant increase in the phenytoin-treated group compared to the control group. A marked infiltration of the positive cells in experimental rats was observed as early as 2 weeks when gingival overgrowth was not fully established. Medullasin-positive cells were mostly neutrophils and partly macrophage-like cells. These findings suggest that medullasin may be involved in mainly host defense and secondarily collagen metabolism in the phenytoin-induced rat model of gingival overgrowth.抄録全体を表示PDF形式でダウンロード (789K) -
Hiroaki Nishio, Yukiko Morimoto, Kazue Hisaoka, Yoshihiro Nakata, Tomo ...専門分野: Infomation Science
2002 年 89 巻 3 号 p. 242-248
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーWe investigated the mechanisms of 5-HT-induced tachycardia, which we reported previously to be triggered by 5-HT3 receptor stimulation, in the isolated guinea pig atrium in comparison with that induced by isoproterenol and histamine. We found that 5-HT-induced tachycardia was completely inhibited by ruthenium red. 5-HT-induced tachycardia was reduced in the capsaicin pre-treated atrium as well as in the presence of capsaicin. The effects of isoproterenol and histamine were not affected by ruthenium red or capsaicin treatment. Furthermore, 5-HT-induced tachycardia was found to be potentiated by thiorphan, an inhibitor of peptide degeneration. Calcitonin gene-related peptide (CGRP) (1 – 37), a full agonist of CGRP1-like receptors, was found to act selectively as a potent stimulator of chronotropic action. CGRP (8 – 37), an antagonist of CGRP1-type receptors, inhibited 5-HT-induced tachycardia as well as effects induced by CGRP (1 – 37). The observation that tetrodotoxin failed to affect 5-HT-induced tachycardia excluded the involvement of 5-hydroxytryptaminergic interneurons. Thus, we confirmed that the mechanism of 5-HT-induced tachycardia is distinct from that induced by isoproterenol and histamine. In conclusion, the activation of 5-HT3 receptors on the sensory nerve terminals brought about ruthenium red-sensitive Ca2+ influx and resulted in the release of CGRP from capsaicin-sensitive stores, and then CGRP stimulated CGRP1-like receptors to produce 5-HT-induced tachycardia.抄録全体を表示PDF形式でダウンロード (346K) -
Masato Tsuboi, Yasuyuki Furukawa, Fumio Kurogouchi, Koichi Nakajima, M ...専門分野: Infomation Science
2002 年 89 巻 3 号 p. 249-254
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーThere is no data about whether botulinum neurotoxin inhibits the parasympathetic ganglionic neurotransmission in the heart, although botulinum toxin as a clinical drug inhibits the release of acetylcholine at the neuromuscular junction. Therefore, we investigated whether botulinum toxin (type A) injected into the sinoatrial (SA) fat pad inhibits decreases in heart rate induced by stimulation of the preganglionic parasympathetic nerves in the heart of the anesthetized dog. Stimulation of the parasympathetic nerves in the SA fat pad (SAP stimulation) prolonged the atrial interval but not the atrioventricular (AV) interval, and cervical vagus nerve stimulation (CV stimulation) prolonged both atrial and AV intervals. After botulinum toxin (20 or 25 mouse units) was injected into the SA fat pad, it gradually inhibited the prolongation of the atrial interval evoked by SAP and CV stimulations but not the prolongation of the AV interval evoked by CV stimulation. Conditioning successive stimulation of the cervical vagus nerves accelerated the inhibition by botulinum toxin of the chronotropic response to CV stimulation. These results indicate that selective injection of botulinum toxin into the SA fat pad blocks bradycardia mediated by parasympathetic ganglionic activation in the dog heart.抄録全体を表示PDF形式でダウンロード (156K) -
Masaya Ito, Yoshiaki Azuma, Hideko Takagi, Keiji Komoriya, Tomohiro Oh ...専門分野: Infomation Science
2002 年 89 巻 3 号 p. 255-266
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーWe investigated the combined effects of alendronate and 1α-hydroxyvitamin D3 (1α(OH)D3) on the bone mass and strength in aged ovariectomized rats and compared them with those of single treatments. Forty-week-old female rats underwent ovariectomy or sham operation, and after 15 weeks, ovariectomized rats were daily administered vehicle alone, alendronate (0.2 or 1.0 mg/kg, p.o.), 1α(OH)D3 (0.02 μg/kg, p.o.), or the combinations of 0.2 or 1.0 mg/kg of alendronate and 1α(OH)D3. After 12 weeks, the groups receiving combined treatments had significantly increased bone density and mechanical strength of the 4th lumbar vertebral body and the midfemur compared to the vehicle-treated group, and the effects were almost equal to or slightly less than the addition of those of the respective single treatments. The increase in mechanical strength was proportional to that in bone mineral density, suggesting that the stimulatory effects of these treatments on bone strength are ascribable primarily to those on bone mass. Analyses of histology, computed tomography, and biochemical markers confirmed the strong effect of the combined treatment on trabecular bone in particular, which was associated with increased trabecular number and decreased bone turnover. We propose that the combination of daily alendronate and 1α(OH)D3 is clinically promising as a curative treatment of established postmenopausal osteoporosis.抄録全体を表示PDF形式でダウンロード (1157K) -
Yune-Fang Ueng, Ming-Jaw Don, Hsiao-Chi Peng, Shu-Yun Wang, Jong-Jing ...専門分野: Infomation Science
2002 年 89 巻 3 号 p. 267-273
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーThe compound herbal medicine Wu-chu-yu-tang is used for the treatment of migraine and vomiting accompanying a cold. To assess the interactions of herb and drug metabolism, effects of Wu-chu-yu-tang on hepatic and renal cytochrome P450 (CYP), UDP-glucuronosyl transferase (UGT) and glutathione S-transferase (GST) were studied in C57BL/6J mice. Treatment of mice with 5 g/kg per day Wu-chu-yu-tang for 3 days caused 2.5-fold and 2.9-fold increases of liver microsomal 7-ethoxyresorufin O-deethylation (EROD) and 7-methoxyresorufin O-demethylation activities, respectively. However, CYP activities toward 7-ethoxycoumarin, benzphetamine, N-nitrosodimethylamine, erythromycin and nifedipine, and conjugation activities of UGT and GST were not affected. In kidney, Wu-chu-yu-tang-treatment had no effects on Cyp, UGT and GST activities. Among the four component herbs of Wu-chu-yu-tang, only Evodiae Fructus (Wu-chu-yu) extract increased EROD activity and CYP1a2 protein level. In E. Fructus, rutaecarpine, evodiamine and dehydroevodiamine are the main active alkaloids. At the doses corresponding to their contents in Wu-chu-yu-tang, rutaecarpine-treatment increased hepatic EROD activity, whereas evodiamine and dehydroevodiamine had no effects. These results demonstrated that ingestion of Wu-chu-yu-tang elevated mouse hepatic Cyp1a2 activity and protein level. E. Fructus and rutaecarpine contributed at least in part to the CYP1a2 induction by Wu-chu-yu-tang. Patients should be cautioned about the drug interaction of Wu-chu-yu-tang and CYP1A2 substrates.抄録全体を表示PDF形式でダウンロード (162K) -
Eiji Kurosaki, Kazuhiro Momose, Ryosuke Nakano, Akiyoshi Shimaya, Taka ...専門分野: Infomation Science
2002 年 89 巻 3 号 p. 274-281
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーWe studied the role of hepatic glycogenesis in glucose intolerance after glucose loading in obese Zucker rats and the effects of YM440 ((Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy}but-2-ene) on it. Lean and obese Zucker rats were treated with YM440 (300 mg/kg) for 14 days and then fasted for 20 h. Thirty percent glucose (0.6 g/kg) or saline was administered intravenously followed by NaH14CO3. Gluconeogenesis was evaluated based on the incorporation of 14C-bicarbonate into blood glucose and hepatic glycogen. Obese rats showed an increase in the incorporation of 14C into blood glucose of 2.5-fold compared to lean rats. The glucose loading decreased the 14C-blood glucose release by 18% in obese rats and 43% in lean rats at 45 min. Glucose loading increased the hepatic glycogen content and 14C incorporation into glycogen in lean but not obese rats. YM440 decreased levels of fasting plasma insulin and blood glucose and the hepatic glycogen content by 50% compared with values for untreated obese rats. After glucose loading, YM440 promoted the incorporation of 14C into glycogen and glycogen synthase activity, leading to an improvement in glucose tolerance. These results indicate that glucose intolerance in obese rats was associated with decreased hepatic glycogenesis and YM440 improved the intolerance by normalizing glycogen metabolism.抄録全体を表示PDF形式でダウンロード (270K) -
Hirofumi Tsuga, Tatsuya Haga, Takeshi Honma専門分野: Infomation Science
2002 年 89 巻 3 号 p. 282-289
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーThe organic solvent toluene is used widely in industry and is toxic to the central nervous system (CNS). To clarify the mechanisms of CNS toxicity following toluene exposure, especially with respect to the G protein-coupling of receptors, we determined the effects of toluene on the activation of Gi by stimulating human muscarinic acetylcholine receptor m2 subtypes (hm2 receptors) expressed in Chinese hamster ovary (CHO) cells. We first examined whether toluene affects the inhibition of adenylyl cyclase by Gi. The attenuation of forskolin-stimulated cAMP formation by the stimulation of hm2 receptors was reduced in a medium containing toluene. Next, we determined the effects of toluene on carbamylcholine-stimulated [35S]GTPγS binding using membrane fractions of CHO cells expressing hm2 receptors. Carbamylcholine-stimulated [35S]GTPγS binding activity was markedly reduced when assayed using reaction buffers containing toluene. However, carbamylcholine-stimulated [35S]GTPγS binding activity was essentially unchanged following pretreatment of the cells with a toluene-saturated medium prior to membrane isolation. Toluene pretreatment and the toluene itself did not alter the characteristics of the binding of carbamylcholine and [3H]N-methylscopolamine to hm2 receptors. On the contrary of the effect of toluene for [35S]GTPγS binding, the effect of toluene for attenuation of forskolin-stimulated cAMP formation by the stimulation of hm2 receptors was irreversible. These observations indicate that toluene acts as an inhibitor of the signal transduction via hm2 receptor stimulation in CHO cells, and at least two mechanisms exist in the inhibition mechanisms by toluene.抄録全体を表示PDF形式でダウンロード (262K) -
Norikazu Sato, Shinji Suzuki, Setsuko Kanai, Minoru Ohta, Atsuo Jimi, ...専門分野: Infomation Science
2002 年 89 巻 3 号 p. 290-295
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーThe synthetic trypsin inhibitor camostat has been used for the treatment of acute and chronic pancreatitis in Japan based on the evidences obtained from a rat experimental model. However, rats differ from other rodents and from humans in terms of lacking a gallbladder and no response of pancreatic bicarbonate secretion to cholecystokinin (CCK). In the present study, we determined whether oral administration of camostat showed a trophic effect in mice as observed in rats and whether the trophic effect, if substantial, was mediated via the CCK-A receptor, using CCK-A receptor gene targeting mice. The chow containing 0.1% camostat was fed to 8-month-old mice. Three- and seven-day treatments with camostat did not affect pancreatic wet weight in CCK-A receptor (+/−) mice. After 14-day treatment, the ratio of pancreatic wet weight/body weight was significantly lower in CCK-A receptor (−/−) than (+/+) mice. The protein and chymotrypsin contents were lower and amylase content was higher in CCK-A receptor (−/−) mice, compared to (+/+) mice. No pathological findings were observed by histological examination. Camostat has a trophic effect on the pancreas in mice and this effect is mediated via the CCK-A receptor, but is less potent than in rats.抄録全体を表示PDF形式でダウンロード (972K) -
Tomokazu Watano, Isao Matsuoka, Junko Kimura専門分野: Infomation Science
2002 年 89 巻 3 号 p. 296-301
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーWe investigated the effects of heavy metal ions on the ATP-induced nonselective cation current through P2X7 receptor (INS · P2X7) in NG108-15 cells using the whole-cell patch-clamp technique. Cu2+ inhibited the INS · P2X7 most potently among the metal ions investigated. Other metals such as Ni2+, Cd2+, Zn2+ and Co2+ also inhibited the INS · P2X7 in concentration-dependent manners. The order of potency was Cu2+ >> Ni2+ > Cd2+ > Zn2+ > Co2+ with IC50 values of 16 nM, 0.79 μM, 1.2 μM, 3.0 μM and 4.6 μM, respectively. Fe3+ (10 and 100 μM) and Mn2+ (10 μM) did not affect the INS · P2X7. A high concentration of Mn2+ (100 μM) slightly inhibited the INS · P2X7. When the concentration-response curve of ATP was obtained in the presence of 3 and 10 nM Cu2+, the maximal response but not the EC50 value appeared to be reduced, suggesting that the inhibition is not competitive. These results suggest that under physiological and toxicological conditions, metal ions, such as Cu2+, Ni2+, Cd2+, Zn2+ and Co2+, may modulate P2X7 receptor channels as inhibitors.抄録全体を表示PDF形式でダウンロード (173K) -
Tomokazu Watano, Isao Matsuoka, Kohei Ogawa, Junko Kimura専門分野: Infomation Science
2002 年 89 巻 3 号 p. 302-308
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーWe investigated the effects of anions on different P2 receptors by measuring ATP-induced increase in intracellular Ca2+ concentration ([Ca2+]i) in fura-2-loaded NG108-15 and PC12 cells. In NG108-15 cells, ATP at 100 μM and 1 mM induced a transient and a sustained [Ca2+]i increase, respectively. The former, but not the latter, was inhibited by U-73122, indicating that the former was via the P2Y2 receptor and the latter via the P2X7 receptor. When external Cl− was replaced by other anions, the [Ca2+]i increase mediated by the P2Y2 receptor was not changed, but that mediated by the P2X7 receptor varied in the order of aspartate− > methanesulfonate− > Cl− > Br ≥ I−. In PC12 cells, transient [Ca2+]i increases mediated by the P2Y2 and P2X2 receptors were not affected by various anions. These results suggest that modulation by anions s unique to the P2X7 receptor and does not occur in P2Y2 and P2X2 receptors. This may be because the mechanism of ATP binding to the P2X7 receptor may be different than that to other P2 receptors.抄録全体を表示PDF形式でダウンロード (296K) -
Tadashi Ishibashi, Junko Wakabayashi, Yukihiro Ohno専門分野: Infomation Science
2002 年 89 巻 3 号 p. 309-315
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーThe effects of a preferential dopamine D3 receptor agonist 7-hydroxy-N,N’-di-n-propyl-2-aminotetralin (7-OH-DPAT) on c-fos mRNA expression in the rat cerebellum were studied by Northern blot analysis. 7-OH-DPAT (0.003 – 10 mg/kg, s.c.) markedly increased c-fos mRNA expression in the cerebellum, while its effects in the striatum, nucleus accumbens, and frontal cortex were negligible. The effect of 7-OH-DPAT on cerebellar c-fos mRNA expression was dose-dependent and statistically significant at doses of 0.3 mg/kg or more. A preferential dopamine D2 agonist, bromocriptine (0.01 – 3 mg/kg, s.c.), failed to increase c-fos mRNA expression in the cerebellum. The effect of 7-OH-DPAT was blocked by two dopamine D2-type-receptor antagonists, haloperidol and perospirone, but not the D1-type-receptor antagonist SCH23390. Furthermore, dopaminergic denervation by 6-hydroxydopamine did not inhibit but rather potentiated the 7-OH-DPAT-induced c-fos mRNA expression in the cerebellum. These findings suggest that 7-OH-DPAT increases c-fos mRNA expression in the rat cerebellum, probably through postsynaptic dopamine D3 receptor activation.抄録全体を表示PDF形式でダウンロード (369K)
Short Communications
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Masaki Saitoh, Atsushi Sugiyama, Tomoo Nakazawa, Keitaro Hashimoto専門分野: Infomation Science
2002 年 89 巻 3 号 p. 316-319
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーHNS-32, an azulene-1-carboxamidine derivative, is an originally synthesized antiarrhythmic compound. Its cardiovascular effects after oral administration (1 – 10 mg/kg) were assessed using the pentobarbital-anesthetized in vivo rat model in comparison with those of verapamil (3 mg/kg, p.o.). Verapamil decreased the heart rate and mean blood pressure and prolonged the PR interval without changing the QRS width (n = 6). Similar results were observed for HNS-32 except that the QRS width was prolonged by the highest dose and the effects occurred slowly and lasted longer. These results suggest that HNS-32 is an orally active slowly-acting calcium plus sodium channel blocker.抄録全体を表示PDF形式でダウンロード (245K) -
Masaaki Miyata, Etsuko Tamura, Yasushi Yamazoe専門分野: Infomation Science
2002 年 89 巻 3 号 p. 320-323
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーAn in vitro system for detection of embryotoxins has been developed by using primary cultures of embryo fibroblasts. Various embryotoxins, including benzo[a]pyrene and thalidomide, have trivial cytotoxicity in embryo fibroblast systems, which is at least in part due to a lack of capacity for metabolic activation. Introduction of steps for microsomal pre-incubation and calcium-precipitation prior to chemical contact resulted in the clear appearance of embryotoxicity toward thalidomide and benzo[a]pyrene. This pre-incubation method will offer advantages for the detection of embryotoxins, which require maternal metabolic activation, and for understanding the mechanisms of their metabolic activations.抄録全体を表示PDF形式でダウンロード (116K)
Rapid Communication
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Yuji Ikegaya, Norio Matsuki専門分野: Infomation Science
2002 年 89 巻 3 号 p. 324-326
発行日: 2002年
公開日: 2002/07/22
ジャーナル フリーThis paper reports that vasopressin is emetogenic in the house musk shrew Suncus murinus. Either intravenous or intracerebroventricular administration of vasopressin caused vomiting within a few minutes. The ED50 of intravenous vasopressin was as high as 4.67 μg/kg, whereas intracerebroventricularly injected vasopressin was effective at a low dose of 20 ng/brain. The emetogenic target of vasopressin may therefore be present in the central nervous system. We propose the Suncus as a useful animal for investigation of vasopressin-mediated emesis, including motion sickness.抄録全体を表示PDF形式でダウンロード (183K)
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