| Project/Area Number |
02671015
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Toho University |
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Principal Investigator |
KOIKE Katsuo Toho Univ.Sch.Pharma.Sci.Associate Prof., 薬学部, 助教授 (70147578)
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| Co-Investigator(Kenkyū-buntansha) |
SHINKAI Michiko Toho Univ.Sch.Pharma.Sci.Assistant, 薬学部, 助手 (60206315)
SATOH Mitsutoshi Toho Univ.Sch.Pharma.Sci.Assistant, 薬学部, 助手 (60231346)
TAKAYANAGI Issei Toho Univ.Sch.Pharma.Sci.Professor, 薬学部, 教授 (70012599)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Beta-adrenoceptor / Partial agonist / Stereoisomer / High affinity site / Low affinity site / Guinea-pig taeaia caecum / Rabbit ciliary body / モルモット盲腸組 / 構造最適化 / β故アドレナリン受容体 / サイクリックAMP / モルモット盲腸紐 / ウサギ毛様体筋 / βーアドレナリン受容体 / 活性作用 / 拮抗作用 |
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| Research Abstract |
The stereoselectivities of beta-adrenergic partial agonists for the high and low affinity binding sites of beta-adrenoceptors were studied. Our results suggest that the high affinity binding site of beta-adrenoceptors is more stereoselective than the low affinity binding site in the guinea-pig taenia caecum. The pA_2-Values of the s(-)-isomers of befunolol and carteolol against S(-)-isoprenaline, which were calculated from the shift of each concentration-response curve in increasing cyclic AMP levels, were significantly larger than those of the R(+)-isomers in the guinea-pig taenia caecum, while the pA_2-values of the S(-)-isomers were not significantly larger than those of the R(+)-isomers in the rabbit ciliary body. The pki-values determined from the binding experiments were in good agreement with the pA_2-values from the increases in cyclic AMP levels. These results suggest that the high affinity binding site of beta-adrenoceptors in the guinea-pig taenia caecum may be able to discriminate stereoselecticity between the R(+)-and S(-)-isomers, while in the rabbit ciliary body there is no stereoselectivity between the two enantiomers.
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