| Autor: |
Karadsheh, Mark S., Shah, M. Salman, Xin Tang, Macdonald, Robert L., Stitzel, Jerry A. |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; Dec2004, Vol. 91 Issue 5, p1138-1150, 13p |
| Abstrakt: |
Mouseα4β2 nicotinic acetylcholine receptors (nAchRs) were stably expressed in HEK293T cells. The function of this stable cell line, termed mmα4β2, was assessed using an aequorin-based luminescence method that measures agonist-evoked changes in intracellular calcium. Agonist-elicited changes in intracellular calcium were due primarily to direct entry of calcium through theα4β2 channel, although release of calcium from intracellular stores contributed˜ 28% of the agonist-evoked response. Agonist pharmacologies were very similar between the mmα4β2 cells and most cell lines that stably express humanα4β2 nAchRs. Based on agonist profiles and sensitivity to the antagonist dihydro-β-erythroidine (DHβE), the predominantα4β2 nAchR expressed in the mmα4β2 cells exhibits a pharmacology that most resembles the DHβE-sensitive component of86Rb+ efflux from mouse brain synaptosomes. However, when evaluated with the aequorin assay, the mmα4β2 nAchR was found to be atypically sensitive to blockade by the presumedα7-selective antagonist methyllycaconitine (MLA), exhibiting an IC50 value of 31 ± 0.1 nm. Similar IC50 values have been reported for the MLA inhibition of nicotine-stimulated dopamine release, a response that is mediated byβ2-subunit-containing nAchRs and notα7-subunit-containing nAchRs. Consequently, at low nanomolar concentrations, MLA may not be as selective forα7-containing nAchRs as previously thought. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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