Activation and blockade by choline of bovine alpha7 and alpha3beta4 nicotinic receptors expressed in oocytes.
Choline, the precursor and the metabolite of acetylcholine, is reputed as a selective alpha7 nicotinic receptor agonist. In this study, however, we have seen that choline exerted a dual effect on bovine nicotinic receptors expressed in Xenopus oocytes. On the one hand, choline behaved as a weak full agonist on bovine alpha7-mediated inward currents, with an EC50 of 0.43 mM. On the other, choline blocked bovine alpha3beta4 currents, with an IC50 of 0.97 mM. The blockade by choline was fast (tau(on), 0.36 s), fully reversible (tau(off), 1.23 s), exhibited voltage-dependence (60% blockade at -100 mV and 30% blockade at -40 mV), and was of a non-competitive nature, suggesting an open-channel type of alpha3beta4 receptor blockade. Thus, choline by activating alpha7 receptors and/or blocking alpha3beta4 receptors might play a physiological role in the control of neurotransmission at cholinergic synapses where alpha7 and alpha3beta4 receptor are expressed.
Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, 28029 Madrid, Spain.
Juana M
JM
González-Rubio
Jonathan
J
Rojo
Laura
L
Tapia
Victoria
V
Maneu
José
J
Mulet
Luis M
LM
Valor
Manuel
M
Criado
Francisco
F
Sala
Antonio G
AG
García
Luis
L
Gandía
D000818:Animals; D002417:Cattle; D002794:Choline / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403530:nicotinic receptor alpha3beta4; D002794:Choline