1995 Fiscal Year Annual Research Report

脳機能に関与するバソプレシン受容体サブタイプの同定から新規脳機能改善薬をめざす

Research Project

Project/Area Number	06557009
Research Institution	Fukuoka University
Principal Investigator	神谷大雄福岡大学, 薬学部, 教授 (90028366)
Co-Investigator(Kenkyū-buntansha)	山村由孝大塚製薬(株)徳島新薬第二研究所, 主任研究員山田勝士鹿児島大学, 医学部付属病院・薬剤部, 教授 (00037491) 本多健治福岡大学, 薬学部, 助手 (60140761) 藤原道弘福岡大学, 薬学部, 教授 (10091331) 高野行夫福岡大学, 薬学部, 助教授 (50113246) 下東康幸九州大学, 理学部, 助教授 (00211293) 斎藤亮福岡大学, 薬学部, 助手 (80122696)
Keywords	バソプレシン受容体 / 脳機能改善薬 / バソプレシン(AVP) / AVP_<4-9> / AVP_<5-8> / V_1受容体拮抗薬 / V_2受容体拮抗薬 / V_2受容体mRNA
Research Abstract	(1)AVP関連ペプチドの合成記憶,学習に高選択的な活性を示す神経ペプチドとして同定されたAVPの誘導体のひとつ[Cystine^6]-AVP5-8 (AVP5-8と略称)のACMシステム含有アナログ2種をデザイン,化学合成した.一方AVP5-8やAVP4-9が結合する特異的な受容体の中枢・脳での検索等のため,AVP4-9の^<35>S放射ラベル誘導体を調整し,HPLCによる精製で化学的に純品として得た.現在,ラット能でのオートラジオグラフィーや結合実験を検討中である. (2)中枢のAVP受容体の関与する生理作用 (1)バソプレシンをラット脳室内に投与すると,胴体回転行動が発現し,その作用はペプチド性V_1受容体拮抗薬で抑制され,V_2受容体拮抗薬では抑制されなかった.非ペプチド性V_1受容体拮抗薬(OPC-21268)およびV_2受容体拮抗薬(OPC-31260)の影響を検討している. (2)AVPの代謝産物の一つであり,記憶障害の改善にAVPよりも有効とされるAVP4-9は,我々の実験で末梢(肝臓)のV1a受容体に結合しないことから,AVP4-9の作用は,中枢の従来のV1/V2受容体でないことをすでに示唆したが,平成7年度は電気生理学的実験も加え,AVP受容体サブタイプの同定を試みつつある. (3)中枢のAVP受容体サブタイプの同定ラット脳のAVP受容体mRNAの発現実験を行い,AVP受容体サブタイプの性質を検討し,同定を試みた.すなわち,生後6-7週令の雄性ラット海馬について行ったRT-PCR法を用いたAVP受容体mRNAの発現実験の結果,V2受容体mRNAの発現を認めた.

Research Products
(23 results)

All Other

All Publications (23 results)

[Publications] Saito, R.: "Vasopressin V1 receptor in rat hippocampus is regulated by adrenocortical systems." Brain Res.646. 170-174 (1994)
[Publications] Honda, K.: "The mechanism of muscarinic agonist-stimulated inositol phosphate formation in permeabilized ileal smooth muscle." Jpn. J. Pharmacol.65. 275-280 (1994)
[Publications] Hirasawa, A.: "Evedence for the existence of vasopressin V2 receptor mRNA in rat hippocampus." Biochem. Biophys. Res. Comm.205. 1702-1706 (1994)
[Publications] Shimohigashi, Y.: "Discriminative affinity labeling of tachykinin NK-1 and NK-3 receptors." Peptide Chemistry. 1993. 337-340 (1994)
[Publications] Shimohigashi, Y.: "Specific interaction of β-amyloid fragments with NK-1 substance P receptors." Peptide Chemistry. 1993. 341-344 (1994)
[Publications] 高野行夫: "循環器調節に対するタキキニン・ペプチドの関与" 循環制御. 15. 283-286 (1994)
[Publications] Honda, K.: "Changes in ^3H-quinuclidinyl benzilate binding and protein synthesis in the striatum following chronic administrations of muscarinic agonist." Jpn. J. Pharmacol.67. 83-86 (1995)
[Publications] Mizuta, A.: "Nitric oxide is a mediator of tachykinin NK3 receptor-induced relaxation in rat mesenteric artery." Br. J. Pharmacol.116. 2919-2922 (1995)
[Publications] Tani, A.: "β-Amyloid fragments with specific conformation with NK-1 substance P receptors" Peptide Chemistry. 1994. 365-368 (1995)
[Publications] Shimohigashi, Y.: "Lysine-49-phospholipases A2 from trimeresurus flavoviridis venom are membrane-acting enzymes" J. Biochem.118. 1037-1044 (1995)
[Publications] Sagara, T.: "Specific affinity labeling of m opioid receptors in rat brain by S-activated sulfhydryldryldihydromorphine analogs." Bioorg. Med. Chem. Lett.5. 1609-1614 (1995)
[Publications] Nose, T.: "Different roles of two consecutive leucine residues in a receptor-tethered ligand peptide (SFLLRNP) in thrombin receptor activation" Bull. Chem. Soc. Jpn.68. 3161-3167 (1995)
[Publications] Kondo, M.: "A tetameric enkephalin analog putative multivalent interaction with opioid receptors" Bull. Chem. Soc. Jpn.68. 3161-3167 (1995)
[Publications] Maeda, I.: "Chymotrypsin inhibition induced by dipeptides with intramolecular CH/π interaction." Peptide Chemistry. 1994. 301-304 (1995)
[Publications] Yasunaga, T.: "Specificity and selectivity in affinity labeling of opioid receptors by cysteamine-containing enkephalin analogs." Peptide Chemistry. 1994. 333-336 (1995)
[Publications] Nose, T.: "Structural requirements of Leu-4 and Arg-5 residues of thrombin receptortethered ligand peptide for receptor activation." Peptide Chemistry. 1994. 365-368 (1995)
[Publications] Shimohigashi, Y.: "π-π interaction between tethered ligand peptide and its binding site in receptor activation." Peptide Chemistry. 1994. 369-372 (1995)
[Publications] Nakamura, K.: "Controlled release of poly-D, L-lactic acid containing bleomycin." Anti-Cancer Drugs. 6. 483-487 (1995)
[Publications] Fujikawa, M.: "Involvement of β-adrenoceptors in regulation of the yawning induced by neuropeptides, oxytocin and α-melanocyte-stimulating hormone, in rats" Pharmacol. Biochem. Behav.50. 339-343 (1995)
[Publications] Kurashima, M.: "Effects of putative dopamine D3 receptor agonists, 7-OH-DPAT, and quinpirole, on yawning, stereotypy, and body temperature in rats." Pharmacol. Biochem. Behav.52. 503-508 (1995)
[Publications] 高野行夫: "タキキニン・ペプチド:基礎研究から臨床応用へ" 福岡大学薬学紀要. 20. 1-8 (1995)
[Publications] Honda, K.: "The involvement of protein kinase C in the muscarinic agonist-induced contractions of guinea pig ileal longitudinal muscle." General Pharmacol.(1996)
[Publications] 高野行夫: "薬業時報社" わかりやすい薬物受容体の基礎(高柳一成編), 10 (1994)

1995 Fiscal Year Annual Research Report

脳機能に関与するバソプレシン受容体サブタイプの同定から新規脳機能改善薬をめざす

Principal Investigator

神谷 大雄 福岡大学, 薬学部, 教授 (90028366)

Research Products

[Publications] Saito, R.: "Vasopressin V1 receptor in rat hippocampus is regulated by adrenocortical systems." Brain Res.646. 170-174 (1994)

[Publications] Honda, K.: "The mechanism of muscarinic agonist-stimulated inositol phosphate formation in permeabilized ileal smooth muscle." Jpn. J. Pharmacol.65. 275-280 (1994)

[Publications] Hirasawa, A.: "Evedence for the existence of vasopressin V2 receptor mRNA in rat hippocampus." Biochem. Biophys. Res. Comm.205. 1702-1706 (1994)

[Publications] Shimohigashi, Y.: "Discriminative affinity labeling of tachykinin NK-1 and NK-3 receptors." Peptide Chemistry. 1993. 337-340 (1994)

[Publications] Shimohigashi, Y.: "Specific interaction of β-amyloid fragments with NK-1 substance P receptors." Peptide Chemistry. 1993. 341-344 (1994)

[Publications] 高野行夫: "循環器調節に対するタキキニン・ペプチドの関与" 循環制御. 15. 283-286 (1994)

[Publications] Honda, K.: "Changes in ^3H-quinuclidinyl benzilate binding and protein synthesis in the striatum following chronic administrations of muscarinic agonist." Jpn. J. Pharmacol.67. 83-86 (1995)

[Publications] Mizuta, A.: "Nitric oxide is a mediator of tachykinin NK3 receptor-induced relaxation in rat mesenteric artery." Br. J. Pharmacol.116. 2919-2922 (1995)

[Publications] Tani, A.: "β-Amyloid fragments with specific conformation with NK-1 substance P receptors" Peptide Chemistry. 1994. 365-368 (1995)

[Publications] Shimohigashi, Y.: "Lysine-49-phospholipases A2 from trimeresurus flavoviridis venom are membrane-acting enzymes" J. Biochem.118. 1037-1044 (1995)

[Publications] Sagara, T.: "Specific affinity labeling of m opioid receptors in rat brain by S-activated sulfhydryldryldihydromorphine analogs." Bioorg. Med. Chem. Lett.5. 1609-1614 (1995)

[Publications] Nose, T.: "Different roles of two consecutive leucine residues in a receptor-tethered ligand peptide (SFLLRNP) in thrombin receptor activation" Bull. Chem. Soc. Jpn.68. 3161-3167 (1995)

[Publications] Kondo, M.: "A tetameric enkephalin analog putative multivalent interaction with opioid receptors" Bull. Chem. Soc. Jpn.68. 3161-3167 (1995)

[Publications] Maeda, I.: "Chymotrypsin inhibition induced by dipeptides with intramolecular CH/π interaction." Peptide Chemistry. 1994. 301-304 (1995)

[Publications] Yasunaga, T.: "Specificity and selectivity in affinity labeling of opioid receptors by cysteamine-containing enkephalin analogs." Peptide Chemistry. 1994. 333-336 (1995)

[Publications] Nose, T.: "Structural requirements of Leu-4 and Arg-5 residues of thrombin receptortethered ligand peptide for receptor activation." Peptide Chemistry. 1994. 365-368 (1995)

[Publications] Shimohigashi, Y.: "π-π interaction between tethered ligand peptide and its binding site in receptor activation." Peptide Chemistry. 1994. 369-372 (1995)

[Publications] Nakamura, K.: "Controlled release of poly-D, L-lactic acid containing bleomycin." Anti-Cancer Drugs. 6. 483-487 (1995)

[Publications] Fujikawa, M.: "Involvement of β-adrenoceptors in regulation of the yawning induced by neuropeptides, oxytocin and α-melanocyte-stimulating hormone, in rats" Pharmacol. Biochem. Behav.50. 339-343 (1995)

[Publications] Kurashima, M.: "Effects of putative dopamine D3 receptor agonists, 7-OH-DPAT, and quinpirole, on yawning, stereotypy, and body temperature in rats." Pharmacol. Biochem. Behav.52. 503-508 (1995)

[Publications] 高野行夫: "タキキニン・ペプチド:基礎研究から臨床応用へ" 福岡大学薬学紀要. 20. 1-8 (1995)

[Publications] Honda, K.: "The involvement of protein kinase C in the muscarinic agonist-induced contractions of guinea pig ileal longitudinal muscle." General Pharmacol.(1996)

[Publications] 高野行夫: "薬業時報社" わかりやすい薬物受容体の基礎(高柳一成編), 10 (1994)

神谷大雄福岡大学, 薬学部, 教授 (90028366)