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A comparison of the...
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Rahman, MoziburUmeå universitet,Obstetrik och gynekologi
(författare)
A comparison of the pharmacological properties of recombinant human and rat α1β2γ2L GABAA receptors in Xenopus oocytes
- Artikel/kapitelEngelska2008
Förlag, utgivningsår, omfång ...
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Wiley,2008
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:umu-36818
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-36818URI
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https://doi.org/10.1111/j.1440-1681.2008.04946.xDOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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In the present study, we compared the pharmacology, particularly neurosteroid modulation of the GABA(A) receptor, between human and rat alpha(1)beta(2)gamma(2)(L) GABA(A) receptors and between human receptors containing the long (L) and short (S) forms of the gamma(2)-subunit. We observed that maximum responses to GABA were significantly higher with the human alpha(1)beta(2)gamma(2)(L) receptor compared with the rat receptor. In terms of neurosteroid modulation, increases in the EC(15) response to GABA induced by 3alpha-OH-5beta-pregnan-20-one (3alpha5betaP), 5alpha-androstane-3alpha,17beta-diol (3alpha5alphaADL) and 5alpha-pregnane-3alpha,20beta-diol (3alpha5alpha-diol) were significantly greater for the rat compared with the human receptor. Responses to 30 micromol/L GABA were inhibited by 3beta-OH-5alpha-pregnan-20-one (UC1010) and 5beta-pregnan-3beta,20(R)-diol (UC1020) to a greater degree for human and rat receptors, respectively. Responses to GABA + 3alpha5alphaTHDOC were inhibited by 5alpha-pregnan-3beta,20(S)-diol (UC1019) and pregnenolone sulphate to a greater degree for human and rat receptors, respectively. The GABA dose-response curves for human alpha(1)beta(2)gamma(2)(S) and alpha(1)beta(2)gamma(2)(L) receptors were identical. However, the maximum GABA-evoked current, the direct gating effect of pentobarbital and the allosteric potentiation of the GABA EC(15) response by 3alpha5alphaTHDOC and 3alpha5betaP were significantly higher with alpha(1)beta(2)gamma(2)(S) than alpha(1)beta(2)gamma(2)(L) receptors. Inhibition of the response to 30 micromol/L GABA by UC1010 and UC1020 was greater for a(1)beta(2)gamma(2)(L) and alpha(1)beta(2)gamma(2)(S) receptors, respectively. Inhibition of responses to 3alpha5alphaTHDOC + GABA by UC1019 and UC1010 was significantly higher for alpha(1)beta(2)gamma(2)(L) receptors. In conclusion, the site of activation by GABA and neurosteroid modulation differ between human and rat alpha(1)beta(2)gamma(2)(L) receptors, as well as between human receptors containing the L and S splice variants of the gamma(2)-subunit.
Ämnesord och genrebeteckningar
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g2L and g2S isoforms;GABA;human and rat a1b2g2L receptors;neurosteroids
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Borra, Vijaya BUmeå universitet,Obstetrik och gynekologi
(författare)
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Isaksson, MonicaUmeå universitet,Obstetrik och gynekologi
(författare)
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Johansson, Inga-MajUmeå universitet,Obstetrik och gynekologi(Swepub:umu)injo0002
(författare)
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Ragagnin, GiannaUmeå universitet,Obstetrik och gynekologi(Swepub:umu)gira0002
(författare)
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Bäckström, TorbjörnUmeå universitet,Obstetrik och gynekologi(Swepub:umu)toba0001
(författare)
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Wang, Ming-DeUmeå universitet,Obstetrik och gynekologi(Swepub:umu)miwa0010
(författare)
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Umeå universitetObstetrik och gynekologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Clinical and experimental pharmacology & physiology: Wiley35:9, s. 1002-10110305-18701440-1681
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