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Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors

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Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors. / Bräuner-Osborne, Hans; Nielsen, B; Krogsgaard-Larsen, P.

I: European Journal of Pharmacology, Bind 350, Nr. 2-3, 05.06.1998, s. 311-6.

Publikation: Bidrag til tidsskriftTidsskriftartikel

Harvard

Bräuner-Osborne, H, Nielsen, B & Krogsgaard-Larsen, P 1998, 'Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors', European Journal of Pharmacology, bind 350, nr. 2-3, s. 311-6.

APA

Bräuner-Osborne, H., Nielsen, B., & Krogsgaard-Larsen, P. (1998). Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors. European Journal of Pharmacology, 350(2-3), 311-6.

Vancouver

Bräuner-Osborne H, Nielsen B, Krogsgaard-Larsen P. Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors. European Journal of Pharmacology. 1998 jun 5;350(2-3):311-6.

Author

Bräuner-Osborne, Hans ; Nielsen, B ; Krogsgaard-Larsen, P. / Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors. I: European Journal of Pharmacology. 1998 ; Bind 350, Nr. 2-3. s. 311-6.

Bibtex

@article{7e7798eae3b0441ba2780b181b357b8c,
title = "Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors",
abstract = "We have studied the effects of the enantiomers of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) and analogues substituted with a methyl, bromo or butyl group in the four position of the ring at cloned metabotropic glutamate (mGlu) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast to the parent compound ibotenic acid, which is a potent group I and II agonist, the (S)-forms of homoibotenic acid and its analogues are selective and potent group I antagonists whereas the (R)-forms are inactive both as agonists and antagonists at group I, II, and III mGlu receptors. Interestingly, (S)-homoibotenic acid and the analogues display equal potency at both mGlu1alpha and mGlu5a with Ki values in the range of 97 to 490 microM, (S)-homoibotenic acid and (S)-2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid [(S)-4-butylhomoibotenic acid] displaying the lowest and highest potency, respectively. The homoibotenic acid analogues thereby differ from mGlu receptor antagonists derived from phenylglycine such as (S)-4-carboxyphenylglycine which only antagonizes mGlu1alpha (Ki = 18 microM) showing no effect at mGlu5a (Ki > 300 microM).",
keywords = "Animals, CHO Cells, Cricetinae, Excitatory Amino Acid Agonists, Ibotenic Acid, Ligands, Receptors, Metabotropic Glutamate, Second Messenger Systems, Stereoisomerism, Structure-Activity Relationship",
author = "Hans Br{\"a}uner-Osborne and B Nielsen and P Krogsgaard-Larsen",
year = "1998",
month = "6",
day = "5",
language = "English",
volume = "350",
pages = "311--6",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "2-3",

}

RIS

TY - JOUR

T1 - Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors

AU - Bräuner-Osborne, Hans

AU - Nielsen, B

AU - Krogsgaard-Larsen, P

PY - 1998/6/5

Y1 - 1998/6/5

N2 - We have studied the effects of the enantiomers of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) and analogues substituted with a methyl, bromo or butyl group in the four position of the ring at cloned metabotropic glutamate (mGlu) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast to the parent compound ibotenic acid, which is a potent group I and II agonist, the (S)-forms of homoibotenic acid and its analogues are selective and potent group I antagonists whereas the (R)-forms are inactive both as agonists and antagonists at group I, II, and III mGlu receptors. Interestingly, (S)-homoibotenic acid and the analogues display equal potency at both mGlu1alpha and mGlu5a with Ki values in the range of 97 to 490 microM, (S)-homoibotenic acid and (S)-2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid [(S)-4-butylhomoibotenic acid] displaying the lowest and highest potency, respectively. The homoibotenic acid analogues thereby differ from mGlu receptor antagonists derived from phenylglycine such as (S)-4-carboxyphenylglycine which only antagonizes mGlu1alpha (Ki = 18 microM) showing no effect at mGlu5a (Ki > 300 microM).

AB - We have studied the effects of the enantiomers of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) and analogues substituted with a methyl, bromo or butyl group in the four position of the ring at cloned metabotropic glutamate (mGlu) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast to the parent compound ibotenic acid, which is a potent group I and II agonist, the (S)-forms of homoibotenic acid and its analogues are selective and potent group I antagonists whereas the (R)-forms are inactive both as agonists and antagonists at group I, II, and III mGlu receptors. Interestingly, (S)-homoibotenic acid and the analogues display equal potency at both mGlu1alpha and mGlu5a with Ki values in the range of 97 to 490 microM, (S)-homoibotenic acid and (S)-2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid [(S)-4-butylhomoibotenic acid] displaying the lowest and highest potency, respectively. The homoibotenic acid analogues thereby differ from mGlu receptor antagonists derived from phenylglycine such as (S)-4-carboxyphenylglycine which only antagonizes mGlu1alpha (Ki = 18 microM) showing no effect at mGlu5a (Ki > 300 microM).

KW - Animals

KW - CHO Cells

KW - Cricetinae

KW - Excitatory Amino Acid Agonists

KW - Ibotenic Acid

KW - Ligands

KW - Receptors, Metabotropic Glutamate

KW - Second Messenger Systems

KW - Stereoisomerism

KW - Structure-Activity Relationship

M3 - Journal article

C2 - 9696422

VL - 350

SP - 311

EP - 316

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2-3

ER -

ID: 45613957