1995 Fiscal Year Annual Research Report

ストレス誘発性胃由来カルシウム調節因子の検索とその生理活性測定法の開発

Research Project

Project/Area Number	07557008
Research Category	Grant-in-Aid for Developmental Scientific Research (B)
Research Institution	Kyushu University
Principal Investigator	粟生修司九州大学, 医学部, 助教授 (40150908)
Co-Investigator(Kenkyū-buntansha)	大村裕日本臓器製薬(株), 生物活性科学研究所, 名誉所長 (30019517) 加藤昌克日本医科大学, 医学部, 助手 (90143239) 立元一彦群馬大学, 生体調節研究所, 教授 (60240694) 片渕俊彦九州大学, 医学部, 講師 (80177401) 堀哲郎九州大学, 医学部, 教授 (00022814)
Keywords	胃由来カルシウム調節因子 / ヒスタミン / 血小板活性化因子 / 細胞内カルシウム / 血液イオン化カルシウム / 胃粘膜固有層 / ストレス / ストレス性低カルシウム血症
Research Abstract	本年度は、1)血液カルシウム低下作用をもつ胃抽出物の分離精製、2)胃由来カルシウム低下因子産生細胞としてのヒスタミン応答細胞の検索、3)胃由来カルシウム低下因子の候補のひとつである血小板活性化因子(PAF)の血液カルシウム調節作用の検討を行った。 1.血液カルシウム低下作用をもつ胃抽出物の分離精製胃抽出物をラットに静脈内投与し、血液イオン化カルシウム濃度を低下させる分画を検索し、その精製作業を行った。粗抽出物のうち1分画に0.05mg-0.25mgの用量で投与30-60分後に血液イオン化カルシウム濃度を約0.05mM低下させる分画を見い出した。しかし、精製を進めるとともに効果の再現性が乏しくなり、最終的に活性分画が消失した。その原因を現在検討中である。 2.胃粘膜固有層ヒスタミン応答細胞の検索胃由来カルシウム低下因子はヒスタミンで分泌が促されることが示唆されている。ヒスタミンの標的細胞を検索するため、本年度は、コラゲナーゼ処理したラット胃粘膜固有層から付着性細胞を単離し、ヒスタミン(1または5mM)に対する一酸化窒素(NO)産生能を酸化還元電位(ボルタメトリー)によるNO測定装置で測定したところ、一酸化窒素の産生が促された。この反応はヒスタミンH2受容体遮断薬やNO合成酵素阻害薬で抑制された。またヒスタミン投与時の細胞内カルシウム濃度をFura-2AMを用いて細胞内カルシウム濃度画像解析装置で測定したところ、ヒスタミンは胃粘膜固有層の付着性細胞の約20%に作用して細胞内Ca2+濃度を軽度上昇させた。粘膜上皮細胞でも調べる必要がある。 3.血小板活性化因子(PAF)の血液カルシウム低下作用 PAF(0.4,1.0,2.0,4.0mg/kg,I.V.)投与前後のラット血液中のイオン化カルシウム濃度をカルシウムイオンメータで経時的に測定した。血小板活性化因子(PAF)の静脈内投与はヒスタミンH2受容体を介さずに低Ca血症を誘発した。一方、ヒスタミンはPAF受容体を介さずに低カルシウム血症を誘発した。ガストリンやヒスタミンで分泌が促される胃由来カルシウム低下因子はPAFではないと考えられる。

Research Products

(48 results)

All Other

All Publications (48 results)

[Publications] Matsui,H: "Central actions of parathyroid hormone on blood calcium and hypothalamic neuronal activity in the rat." Am.J.Physiol.268. R21-R27 (1995)
[Publications] Oka,T.: "The opposing effects of interleukin-1β microinjected into the preoptic hypothalamus and the ventromdial hypothalamus on nociceptive behavior in rats." Brain Res.700. 271-278 (1995)
[Publications] Aou,S.: "Hypothalamus regulates calcium metabolism in rats." Neurobiology. (in press).
[Publications] Aou,S.: "Hypothalamo-vagal control of calcium metabolism in rats." J.Auton.Nerv.Syst.(in press).
[Publications] Suzuki,K.: "Repetitively firing neurons in the rat medial nucleus tractus solitarius is invoved in cholecystokinin type-A receptor mediated functions." J.Auton.Nerv.Syst.(in press).
[Publications] Li,A.-J.: "Fibroblast growthfactor receptor-1 in the lateral hypothalanic area regulates food intake." Exp.Neurol.(in press).
[Publications] 粟生修司: "視床下部を中心とする性行動・情動行動制御機構:視床下部機能の新しい側面." 日本生理誌. 57増刊号. 155-163 (1995)
[Publications] 粟生修司: "肥満症、II.摂食、食欲調節系、摂食、食欲調節系概論." 日本臨床. 53. 13-18 (1995)
[Publications] 粟生修司: "肥満症、II.摂食、食欲調節系、調節因子概論" 日本臨床. 53. 19-25 (1995)
[Publications] 粟生修司: "肥満症、II.摂食、食欲調節系、調節因子の受容体と作用機序:グルコース(グルコース受容ニューロン、グルコース感受性ニューロン)." 日本臨床. 53. 26-32 (1995)
[Publications] 粟生修司: "肥満症、II.摂食、食欲調節系、調節因子の受容体と作用機序:その他の有機化合物(有機酸、ラクトンなど)." 日本臨床. 53. 85-89 (1995)
[Publications] Nakashima,T.: "Naloxone suppresses the rising phase of fever induced by interferon α." Brain.Res.Bull.37. 61-66 (1995)
[Publications] Take,S.: "Interferon-α acts at the preoptic hypothalamus to reduce natural killer cytotoxicity in rats." American Journal of Physiology. 268. R1406-R1410 (1995)
[Publications] Niijima,A.: "The effect of interleukin-1β on the efferent activity of the vagus nerve to the thymus." Journal of the Autonomic Nervous System. 54. 137-144 (1995)
[Publications] Ando,T.: "Intracerebroventricular injection of prostaglandin E2 increases splenic sympathetic nerve activity in rats." American Journal of Physiology. 269. R662-R668 (1995)
[Publications] Uchimura,D.: "Facilitatory effects of pituitary adenylate cyclase activating polypeptide (PACAP) on neurons in the magnocellular portion of the rat hypothalamic paraventricular nucleus (PVN) in vitro." Journal of Neuroendocrinology. 8. 137-143 (1995)
[Publications] Katafichi,T.: "Cerebellar afferents to neuroendocrine cells:implications for adaptive responses to simulated weightlessness." Endocrine Journal. 42. 729-737 (1995)
[Publications] Oka,T.: "Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats." Brain Res.692. 123-128 (1995)
[Publications] 堀哲郎: "免疫系連関と発熱." 第24回日本医学会総会会誌. II. 538-539 (1995)
[Publications] 堀哲郎: "脳・免疫系連関と発熱." 臨床と研究72. 72. 2381-2386 (1995)
[Publications] Katafichi,T.: "Roles of cytokines in the neural-immune interactions:modulation of NMDA responses by IFNα" Neurobiology. (in press). (1996)
[Publications] Hori,T.: "The hypothalamo-sympathetic nervous system modulates peripheral cellular immunity." Neurobiology. (in press). (1996)
[Publications] Hori,T.: "The autonomic nervous system as a communication channel between the brain and the immune system." Neuroimmunomodulation. (in press). (1996)
[Publications] 片渕俊彦: "脳-免疫系連関とサイトカイン.免疫疾患-state of arts." 医学のあゆみ. 別冊. 94-97 (1995)
[Publications] 片渕俊彦: "交感神経系を介する免疫調節." 第24回日本医学会総会会誌. III. 79- (1995)
[Publications] Kubohara,Y.: "Putative morphogen,DIF,of dietyostelium discoideum induces apoptosis in rat pancreatic AR42J cells." Develop.Growth Differ.359. 119-122 (1995)
[Publications] Kubohara,Y.: "Differentiation-inducing factor of D.discoideum raises intracellular calcium concentration and suppresses cell growth in rat pancreatic AR42J cells" FEBS Letters. 359. 119-122 (1995)
[Publications] Ishikawa,K.: "Meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy" Brain Research. 677. 20-28 (1995)
[Publications] Suzuki,S.: "Isolation and characterization of novel antimicrobial peptides,rugosins,A,B,and C from the skin of the frog,rana rugosa." Biochem.Biophys.Res.Commun.212. 249-254 (1995)
[Publications] Ishikawa,K.: "Meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy" Brain Research. 697. 122-129 (1995)
[Publications] Herzig,K-H.: "Diazepam biding inhibitors is a potent cholecystokinin releasing peptide in the intestine." Proc.Natl.Acad.Sci.USA. (in press).
[Publications] Kato,M.: "Growth hormone relaeasing hormone (GFR) augments the voltage-gated sodium current in cultured rat pituitary cells" Am.J.Physiol.270. C125-C130 (1995)
[Publications] Kato,M.: "Withdrawal of somatostatin augments L-type Ca2+ current in primary cultured rat somatotrophs." J.Neurondocrinology. 7. 855-859 (1995)
[Publications] Kato,M.: "GLP-1 depolarizes rat pancreatic β cells in a Na+ dependent manner" Regulatory Peptides. (in press).
[Publications] Ma,H.: "Effects of a pancreastatin and somatostatin on secretagogue-induced rise in intracellular free calcium in single rat pancreatic islet cells." Regulatory Peptides. (in press).
[Publications] Saito,Y.: "Effects of bradykinin on the intrcellular calcium concentration of pancreatic acinar AR42J cells" Life Science. (in press).
[Publications] Sasaki,K.: "An amino-fragment peptide of acidic fibroblast growth factor modulates synaptic transmission in rat hippocampal slices." Brain Res.Bull.38. 185-191 (1995)
[Publications] Oomura,Y.: "Acidic fibroblast growth factor protects memory and immunoreactivity impairment in senessence accelerated mice." Neurobiology. 3. 371-380 (1995)
[Publications] Sasaki,K.: "Effect of acidic bibroblast growth factor on neuronal activity of the parvocellular part in rat paraventricular nucelus." Neurobiology. 3. 329-338 (1995)
[Publications] Sasaki,K.: "Action of acidic bibroblast growth factor fragments on food intake in rats." Obesity Res.3,suppl.5. 697s-706s (1995)
[Publications] 大村裕: "食事と脳" 肥満研究. 1. 3-7 (1995)
[Publications] 大村裕: "線維芽細胞成長因子(FGF)-神経栄養因子-update." Clinical Neuroscience. 13. 800-804 (1995)
[Publications] 粟生修司: "視床下部〔神経科学の基礎と臨床IV〕" ブレーン出版, 171 (1995)
[Publications] 粟生修司: "心身医学標準テキスト" 医学書院(印刷中),
[Publications] 大村裕: "脳機能の解明-分子から病態まで" 創風社, 286 (1995)
[Publications] Hori,T.: "Physiological Basis of Occupational Health:Streesful Environments" SPB Academic Publishing(in press), (1996)
[Publications] 堀哲郎: "脳と免疫" 共立出版, 195 (1995)
[Publications] 片渕俊彦: "脳と免疫-脳と生体防御系との関わりあい(第5章)" 共立出版, 195 (1995)

1995 Fiscal Year Annual Research Report

ストレス誘発性胃由来カルシウム調節因子の検索とその生理活性測定法の開発

Principal Investigator

粟生 修司 九州大学, 医学部, 助教授 (40150908)

Research Products

[Publications] Matsui,H: "Central actions of parathyroid hormone on blood calcium and hypothalamic neuronal activity in the rat." Am.J.Physiol.268. R21-R27 (1995)

[Publications] Oka,T.: "The opposing effects of interleukin-1β microinjected into the preoptic hypothalamus and the ventromdial hypothalamus on nociceptive behavior in rats." Brain Res.700. 271-278 (1995)

[Publications] Aou,S.: "Hypothalamus regulates calcium metabolism in rats." Neurobiology. (in press).

[Publications] Aou,S.: "Hypothalamo-vagal control of calcium metabolism in rats." J.Auton.Nerv.Syst.(in press).

[Publications] Suzuki,K.: "Repetitively firing neurons in the rat medial nucleus tractus solitarius is invoved in cholecystokinin type-A receptor mediated functions." J.Auton.Nerv.Syst.(in press).

[Publications] Li,A.-J.: "Fibroblast growthfactor receptor-1 in the lateral hypothalanic area regulates food intake." Exp.Neurol.(in press).

[Publications] 粟生修司: "視床下部を中心とする性行動・情動行動制御機構:視床下部機能の新しい側面." 日本生理誌. 57増刊号. 155-163 (1995)

[Publications] 粟生修司: "肥満症、II.摂食、食欲調節系、摂食、食欲調節系概論." 日本臨床. 53. 13-18 (1995)

[Publications] 粟生修司: "肥満症、II.摂食、食欲調節系、調節因子概論" 日本臨床. 53. 19-25 (1995)

[Publications] 粟生修司: "肥満症、II.摂食、食欲調節系、調節因子の受容体と作用機序:グルコース(グルコース受容ニューロン、グルコース感受性ニューロン)." 日本臨床. 53. 26-32 (1995)

[Publications] 粟生修司: "肥満症、II.摂食、食欲調節系、調節因子の受容体と作用機序:その他の有機化合物(有機酸、ラクトンなど)." 日本臨床. 53. 85-89 (1995)

[Publications] Nakashima,T.: "Naloxone suppresses the rising phase of fever induced by interferon α." Brain.Res.Bull.37. 61-66 (1995)

[Publications] Take,S.: "Interferon-α acts at the preoptic hypothalamus to reduce natural killer cytotoxicity in rats." American Journal of Physiology. 268. R1406-R1410 (1995)

[Publications] Niijima,A.: "The effect of interleukin-1β on the efferent activity of the vagus nerve to the thymus." Journal of the Autonomic Nervous System. 54. 137-144 (1995)

[Publications] Ando,T.: "Intracerebroventricular injection of prostaglandin E2 increases splenic sympathetic nerve activity in rats." American Journal of Physiology. 269. R662-R668 (1995)

[Publications] Uchimura,D.: "Facilitatory effects of pituitary adenylate cyclase activating polypeptide (PACAP) on neurons in the magnocellular portion of the rat hypothalamic paraventricular nucleus (PVN) in vitro." Journal of Neuroendocrinology. 8. 137-143 (1995)

[Publications] Katafichi,T.: "Cerebellar afferents to neuroendocrine cells:implications for adaptive responses to simulated weightlessness." Endocrine Journal. 42. 729-737 (1995)

[Publications] Oka,T.: "Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats." Brain Res.692. 123-128 (1995)

[Publications] 堀 哲郎: "免疫系連関と発熱." 第24回日本医学会総会会誌. II. 538-539 (1995)

[Publications] 堀 哲郎: "脳・免疫系連関と発熱." 臨床と研究72. 72. 2381-2386 (1995)

[Publications] Katafichi,T.: "Roles of cytokines in the neural-immune interactions:modulation of NMDA responses by IFNα" Neurobiology. (in press). (1996)

[Publications] Hori,T.: "The hypothalamo-sympathetic nervous system modulates peripheral cellular immunity." Neurobiology. (in press). (1996)

[Publications] Hori,T.: "The autonomic nervous system as a communication channel between the brain and the immune system." Neuroimmunomodulation. (in press). (1996)

[Publications] 片渕俊彦: "脳-免疫系連関とサイトカイン.免疫疾患-state of arts." 医学のあゆみ. 別冊. 94-97 (1995)

[Publications] 片渕俊彦: "交感神経系を介する免疫調節." 第24回日本医学会総会会誌. III. 79- (1995)

[Publications] Kubohara,Y.: "Putative morphogen,DIF,of dietyostelium discoideum induces apoptosis in rat pancreatic AR42J cells." Develop.Growth Differ.359. 119-122 (1995)

[Publications] Kubohara,Y.: "Differentiation-inducing factor of D.discoideum raises intracellular calcium concentration and suppresses cell growth in rat pancreatic AR42J cells" FEBS Letters. 359. 119-122 (1995)

[Publications] Ishikawa,K.: "Meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy" Brain Research. 677. 20-28 (1995)

[Publications] Suzuki,S.: "Isolation and characterization of novel antimicrobial peptides,rugosins,A,B,and C from the skin of the frog,rana rugosa." Biochem.Biophys.Res.Commun.212. 249-254 (1995)

[Publications] Ishikawa,K.: "Meninges play a neurotrophic role in the regeneration of vasopressin nerves after hypophysectomy" Brain Research. 697. 122-129 (1995)

[Publications] Herzig,K-H.: "Diazepam biding inhibitors is a potent cholecystokinin releasing peptide in the intestine." Proc.Natl.Acad.Sci.USA. (in press).

[Publications] Kato,M.: "Growth hormone relaeasing hormone (GFR) augments the voltage-gated sodium current in cultured rat pituitary cells" Am.J.Physiol.270. C125-C130 (1995)

[Publications] Kato,M.: "Withdrawal of somatostatin augments L-type Ca2+ current in primary cultured rat somatotrophs." J.Neurondocrinology. 7. 855-859 (1995)

[Publications] Kato,M.: "GLP-1 depolarizes rat pancreatic β cells in a Na+ dependent manner" Regulatory Peptides. (in press).

[Publications] Ma,H.: "Effects of a pancreastatin and somatostatin on secretagogue-induced rise in intracellular free calcium in single rat pancreatic islet cells." Regulatory Peptides. (in press).

[Publications] Saito,Y.: "Effects of bradykinin on the intrcellular calcium concentration of pancreatic acinar AR42J cells" Life Science. (in press).

[Publications] Sasaki,K.: "An amino-fragment peptide of acidic fibroblast growth factor modulates synaptic transmission in rat hippocampal slices." Brain Res.Bull.38. 185-191 (1995)

[Publications] Oomura,Y.: "Acidic fibroblast growth factor protects memory and immunoreactivity impairment in senessence accelerated mice." Neurobiology. 3. 371-380 (1995)

[Publications] Sasaki,K.: "Effect of acidic bibroblast growth factor on neuronal activity of the parvocellular part in rat paraventricular nucelus." Neurobiology. 3. 329-338 (1995)

[Publications] Sasaki,K.: "Action of acidic bibroblast growth factor fragments on food intake in rats." Obesity Res.3,suppl.5. 697s-706s (1995)

[Publications] 大村 裕: "食事と脳" 肥満研究. 1. 3-7 (1995)

[Publications] 大村 裕: "線維芽細胞成長因子(FGF)-神経栄養因子-update." Clinical Neuroscience. 13. 800-804 (1995)

[Publications] 粟生修司: "視床下部〔神経科学の基礎と臨床IV〕" ブレーン出版, 171 (1995)

[Publications] 粟生修司: "心身医学標準テキスト" 医学書院(印刷中),

[Publications] 大村 裕: "脳機能の解明-分子から病態まで" 創風社, 286 (1995)

[Publications] Hori,T.: "Physiological Basis of Occupational Health:Streesful Environments" SPB Academic Publishing(in press), (1996)

[Publications] 堀 哲郎: "脳と免疫" 共立出版, 195 (1995)

[Publications] 片渕俊彦: "脳と免疫-脳と生体防御系との関わりあい(第5章)" 共立出版, 195 (1995)

粟生修司九州大学, 医学部, 助教授 (40150908)

[Publications] 堀哲郎: "免疫系連関と発熱." 第24回日本医学会総会会誌. II. 538-539 (1995)

[Publications] 堀哲郎: "脳・免疫系連関と発熱." 臨床と研究72. 72. 2381-2386 (1995)

[Publications] 大村裕: "食事と脳" 肥満研究. 1. 3-7 (1995)

[Publications] 大村裕: "線維芽細胞成長因子(FGF)-神経栄養因子-update." Clinical Neuroscience. 13. 800-804 (1995)

[Publications] 大村裕: "脳機能の解明-分子から病態まで" 創風社, 286 (1995)

[Publications] 堀哲郎: "脳と免疫" 共立出版, 195 (1995)