Pharmacological properties of rat α7 nicotinic receptors expressed in native and recombinant cell systems

• Published in: European journal of pharmacology Vol. 445; no. 3; pp. 153 - 161
• Main Authors: Virginio, Caterina, Giacometti, Angelo, Aldegheri, Laura, Rimland, Joseph M, Terstappen, Georg C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 12.06.2002; Elsevier
• Subjects: Biological and medical sciences; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; GH4C1 cell; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Nicotinic acetylcholine receptor; PC12 cell; Perforated patch-clamp; Recombinant expression; α7 Subunit; PC12 cell; Recombinant expression; GH4C1 cell; α7 Subunit; Perforated patch-clamp; Nicotinic acetylcholine receptor; Rat; Rodentia; Electrophysiology; Subunit; In vitro; Polymerase chain reaction; Vertebrata; Cholinergic receptor; Mammalia; Structure activity relation; Animal; Established cell line; α7 nicotinic receptor; Models; Recombinant protein
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)01750-8

The pharmacological properties of the rat α7 nicotinic acetylcholine receptor endogenously expressed in PC12 cells and recombinantly expressed in GH4C1 cells (α7-GH4C1 cells) were characterized and compared. Patch-clamp recordings demonstrated that activation by choline and block by methyllycaconitine and dihydro-β-erythroidine were similar, but block by mecamylamine was different. Whereas in α7-GH4C1 cells the inhibition curve for mecamylamine was monophasic (IC 50 of 1.6 μM), it was biphasic in PC12 cells (IC 50 values of 341 nM and 9.6 μM). 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-β-erythroidine differentially blocked acetylcholine-evoked currents in both systems. Since reverse transcriptase polymerase chain reaction (RT-PCR) experiments revealed expression of α3, α4, α5, α7 and β4 subunits in PC12 cells, whereas GH4C1 cells express only the β4 subunit, our results suggest that more than one form of α7 containing heteromeric nicotinic receptors might be functionally expressed in PC12 cells.