2000 Fiscal Year Annual Research Report

アドレノメデュリン・ファミリーの生理機能と遺伝子発現:培養副腎髄質細胞と摘出血管

Research Project

Project/Area Number	10218206
Research Institution	宮崎医科大学
Principal Investigator	和田明彦宮崎医科大学, 医学部, 教授 (30131949)
Co-Investigator(Kenkyū-buntansha)	柳田俊彦宮崎医科大学, 医学部, 助手 (60295227) 上園保仁長崎大学, 医学部, 講師 (20213340) 小林英幸宮崎医科大学, 医学部, 助教授 (40148953) 山本隆一九州保健福祉大学, 保健科学部, 教授 (10094111)
Keywords	Adrenomedullin family / Adrenal chromaffin cells / Choroid plexus / Uterus / Exocytosis / Tyrosine hydroxylase / Nicotinic receptors / Autocrine regulation
Research Abstract	1.副腎髄質細胞のPAMPファミリーウシ副腎髄質クロマフィン細胞からPAMPファミリーのペプチドを分離精製し、PAMP20の他、新たにPAMP12とPAMP16を同定した。これらのPAMPは、細胞からカテコールアミンとともに、ニコチン受容体刺激により開口分泌された。PAMP12は、ニコチン受容体を非競合的に阻害し、カテコールアミン分泌を抑制したが、電位依存性Ca^<2+>チャネルの活性化、またはヒスタミン受容体刺激によるカテコールアミン分泌には影響を及ぼさなかった。また、PAMP12は、カテコールアミン合成の律速酵素であるチロシン水酸化酵素の活性化を抑制し、カテコールアミン合成をも調節することを明らかにした。 2.脈絡叢のAM受容体 AMは、CGRPより強力に、ラット脈絡叢のcAMPを増加させた。RT-PCR法によりAM受容体のmRNAを解析すると、CRLRとRAMP-2のmRNAの発現が高く、これがAMに特異的な受容体を形成していることが示唆された。また、AMのmRNAの発現も高く、AMは脈絡叢で合成・分泌され、脈絡叢にオートクリン的に作用する調節因子であることが示唆された。 3.ラット摘出子宮平滑筋 AMは、子宮の自発的収縮とブラジキニンによる収縮を濃度依存的に抑制し、これは、AM[22-52],CGRP[8-37]のいづれによっても阻止された。他方、オキシトシン、プロスタグランディンF_<2α>による収縮は、AMにより影響されなかった。RT-PCR法により、子宮平滑筋にAM,CRLR,RAMP-1,-2,-3のmRNAが発現していることを示した。妊娠に伴ない子宮でのAM,AMmRNA発現量は、胎盤付着部の脱落膜組織に限局して著しく増加した。これらの結果から、AMが胎盤付着部の子宮収縮を抑制することにより、妊娠の維持に重要な役割を果たしている可能性が、示唆された。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Toshihiko Yanagita et al.: "Adrenomedullin inhibits spontaneous and bradykinin-induced but not oxytocin- or prostaglandin F2α-induced periodic contraction of rat uterus."British Journal of Pharmacology. 130. 1727-1730 (2000)
[Publications] Hideyuki Kobayashi et al.: "Adrenomedullin receptors in rat cerebral microvessels."Molecular Brain Research. 81. 1-6 (2000)
[Publications] Hideyuki Kobayashi et al.: "Regulation of synthesis and release of adrenomedullin and proadrenomedullin Nterminal 20 peptide by cyclic AMP-dependent protein kinase pathway in bovine adrenal chromaffin cells."International Symposium on Neuronal Signaling and Protein Phosphorylation-Dephosphorylation. 152 (2000)
[Publications] Yasuhito Uezono et al.: "Adrenomedullin inhibits platelet-derived growth factor-or ATP-induced DNA synthesis in an autocrine/paracrine manner in human glial cell line KG-1C."Society for Neuroscience (30th Annual Meeting). 26(Abstract). 382 (2000)
[Publications] Hideyuki Kobayashi et al.: "Gene expression of adrenomedullin receptors in rat cerebral microvessels."Society for Neuroscience (30th Annual Meeting). 26(Abstract). 382 (2000)
[Publications] Toshihiko Yanagita et al.: "A novel role of adrenomedullin in the regulation of rat uterine contractility."Second International Symposium on Adrenomedullin and PAMP. 39 (2000)
[Publications] Hideyuki Kobayashi et al.: "Regulation of catecholamine release and synthesis by PAMP."Second International Symposium on Adrenomedullin and PAMP. 42 (2000)
[Publications] Hideyuki Kobayashi et al.: "Receptors specific for adrenomedullin in rat cerebral microvessels."Second International Symposium on Adrenomedullin and PAMP. 61 (2000)
[Publications] Yoshikazu Uchikawa et al.: "A possible role of adrenomedullin in the isolated bovine ires sphincter muscle contractility."Second International Symposium on Adrenomedullin and PAMP. 68 (2000)
[Publications] Hideyuki Kobayashi et al.: "Adrenomedullin receptors in rat choroid plexus."Neuroscience Letters. 297. 167-170 (2001)
[Publications] Hideyuki Kobayashi et al.: "Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells."Molecular Brain Research. 87. 175-183 (2001)
[Publications] Toshihiko Yanagita et al.: "Regulation of uterine contractility by adrenomedullin."Japanese Journal of Pharmaclogy. 85(Suppl.I). 27 (2001)
[Publications] Ryuichi Yamamoto et al.: "The role of adrenomedullin in the regulation of bovine pupillary size."Japanese Journal of Pharmaclogy. 85(Suppl.I). 136 (2001)
[Publications] Yasuhito Uezono et al.: "Adrenomedullin suppresses platelet-derived growth factor-or extracellular ATP-induced cell proliferation through activation of protein kinase A in human oligodendroglial KG-1C cells."Japanese Journal of Pharmaclogy. 85(Suppl.I). 137 (2001)
[Publications] Hideyuki Kobayashi et al.: "Adrenomedullin receptors in rat choroid plexus."Japanese Journal of Pharmaclogy. 85(Suppl.I). 137 (2001)

2000 Fiscal Year Annual Research Report

アドレノメデュリン・ファミリーの生理機能と遺伝子発現:培養副腎髄質細胞と摘出血管

Principal Investigator

和田 明彦 宮崎医科大学, 医学部, 教授 (30131949)

Research Products

[Publications] Toshihiko Yanagita et al.: "Adrenomedullin inhibits spontaneous and bradykinin-induced but not oxytocin- or prostaglandin F2α-induced periodic contraction of rat uterus."British Journal of Pharmacology. 130. 1727-1730 (2000)

[Publications] Hideyuki Kobayashi et al.: "Adrenomedullin receptors in rat cerebral microvessels."Molecular Brain Research. 81. 1-6 (2000)

[Publications] Yasuhito Uezono et al.: "Adrenomedullin inhibits platelet-derived growth factor-or ATP-induced DNA synthesis in an autocrine/paracrine manner in human glial cell line KG-1C."Society for Neuroscience (30th Annual Meeting). 26(Abstract). 382 (2000)

[Publications] Hideyuki Kobayashi et al.: "Gene expression of adrenomedullin receptors in rat cerebral microvessels."Society for Neuroscience (30th Annual Meeting). 26(Abstract). 382 (2000)

[Publications] Toshihiko Yanagita et al.: "A novel role of adrenomedullin in the regulation of rat uterine contractility."Second International Symposium on Adrenomedullin and PAMP. 39 (2000)

[Publications] Hideyuki Kobayashi et al.: "Regulation of catecholamine release and synthesis by PAMP."Second International Symposium on Adrenomedullin and PAMP. 42 (2000)

[Publications] Hideyuki Kobayashi et al.: "Receptors specific for adrenomedullin in rat cerebral microvessels."Second International Symposium on Adrenomedullin and PAMP. 61 (2000)

[Publications] Yoshikazu Uchikawa et al.: "A possible role of adrenomedullin in the isolated bovine ires sphincter muscle contractility."Second International Symposium on Adrenomedullin and PAMP. 68 (2000)

[Publications] Hideyuki Kobayashi et al.: "Adrenomedullin receptors in rat choroid plexus."Neuroscience Letters. 297. 167-170 (2001)

[Publications] Hideyuki Kobayashi et al.: "Selective inhibition of nicotinic cholinergic receptors by proadrenomedullin N-terminal 12 peptide in bovine adrenal chromaffin cells."Molecular Brain Research. 87. 175-183 (2001)

[Publications] Toshihiko Yanagita et al.: "Regulation of uterine contractility by adrenomedullin."Japanese Journal of Pharmaclogy. 85(Suppl.I). 27 (2001)

[Publications] Ryuichi Yamamoto et al.: "The role of adrenomedullin in the regulation of bovine pupillary size."Japanese Journal of Pharmaclogy. 85(Suppl.I). 136 (2001)

[Publications] Yasuhito Uezono et al.: "Adrenomedullin suppresses platelet-derived growth factor-or extracellular ATP-induced cell proliferation through activation of protein kinase A in human oligodendroglial KG-1C cells."Japanese Journal of Pharmaclogy. 85(Suppl.I). 137 (2001)

[Publications] Hideyuki Kobayashi et al.: "Adrenomedullin receptors in rat choroid plexus."Japanese Journal of Pharmaclogy. 85(Suppl.I). 137 (2001)

和田明彦宮崎医科大学, 医学部, 教授 (30131949)