Pharmacological properties of rat alpha 7 nicotinic receptors expressed in native and recombinant cell systems.
The pharmacological properties of the rat alpha7 nicotinic acetylcholine receptor endogenously expressed in PC12 cells and recombinantly expressed in GH4C1 cells (alpha7-GH4C1 cells) were characterized and compared. Patch-clamp recordings demonstrated that activation by choline and block by methyllycaconitine and dihydro-beta-erythroidine were similar, but block by mecamylamine was different. Whereas in alpha7-GH4C1 cells the inhibition curve for mecamylamine was monophasic (IC(50) of 1.6 microM), it was biphasic in PC12 cells (IC(50) values of 341 nM and 9.6 microM). The same rank order of potency was obtained for various nicotinic agonists, while acetylcholine was 3.7-fold less potent and 1.5-fold more effective in PC12 cells. Dihydro-beta-erythroidine differentially blocked acetylcholine-evoked currents in both systems. Since reverse transcriptase polymerase chain reaction (RT-PCR) experiments revealed expression of alpha3, alpha4, alpha5, alpha7 and beta4 subunits in PC12 cells, whereas GH4C1 cells express only the beta4 subunit, our results suggest that more than one form of alpha7 containing heteromeric nicotinic receptors might be functionally expressed in PC12 cells.
Virginio
Caterina
C
Systems Research, GlaxoSmithKline Medicines Research Centre, Via A. Fleming 4, 37135, Verona, Italy. CV49987@gsk.com
Giacometti
Angelo
A
Aldegheri
Laura
L
Rimland
Joseph M
JM
Terstappen
Georg C
GC
D000818:Animals; D004305:Dose-Response Relationship, Drug; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D011978:Receptors, Nicotinic / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor