Article ID Journal Published Year Pages File Type
2534645 European Journal of Pharmacology 2009 8 Pages PDF
Abstract

Mouse Beta-TC6 insulinoma cells possessing nicotinic receptor [Ohtani, M., Oka, T., Badyuk, M., Xiao, Y., Kellar, KJ., Daly, JW., 2006. Mouse β-TC6 insulinoma cells: high expression of functional α3β4 nicotinic receptors mediating membrane potential, intracellular calcium, and insulin release. Mol. Pharmacol. 69, 899–907.] also expressed M3 and M4 muscarinic receptors. Carbamylcholine, a mixed muscarinic/nicotinic receptor agonist, or oxotremorine M, a selective muscarinic agonist, elicited an elevation of cytoplasmic Ca2+ concentration ([Ca2+]i) and release of insulin. The maximal [Ca2+]i response induced by carbamylcholine was larger than that of oxotremorine M or that of nicotine, suggesting that carbamylcholine enhanced the [Ca2+]i response by stimulating two types of receptor. M3 and M4 muscarinic receptor antagonists inhibited the [Ca2+]i responses to carbamylcholine and oxotremorine M, suggesting the involvement of these muscarinic receptors in the regulation of [Ca2+]i. In addition, pretreatment with carbamylcholine inhibited the [Ca2+]i responses to oxotremorine M or nicotine, indicating that the effect of carbamylcholine on [Ca2+]i was mediated by both muscarinic and nicotinic receptors. A phospholipase C (PLC) inhibitor U73122, a protein kinase C (PKC) inhibitor chelerythrine and a phospholipase A2 (PLA2) inhibitor AACOCF3 inhibited the [Ca2+]i response to carbamylcholine or oxotremorine M, while these inhibitors did not block the effect of nicotine. Carbamylcholine induced a smaller extent of insulin secretion than oxotremorine M, suggesting that concomitant stimulation of muscarinic and nicotinic receptors by carbamylcholine resulted in the negative type of the receptor interaction.

Related Topics
Life Sciences Neuroscience Cellular and Molecular Neuroscience
Authors
, , ,