| 19109944 |
Ohtani M, Daly JW, Oka T: Co-existence of muscarinic and nicotinic receptors and their functional interaction in mouse Beta-TC6 cells. Eur J Pharmacol. 2009 Feb 14;604(1-3):150-7. Epub 2008 Dec 16.
Mouse Beta-TC6 insulinoma cells possessing nicotinic receptor [Ohtani, M., Oka, T., Badyuk, M., Xiao, Y., Kellar, KJ., Daly, JW., 2006. Mouse beta-TC6 insulinoma cells: high expression of functional alpha3beta4 nicotinic receptors mediating membrane potential, intracellular calcium, and insulin release. Mol. Pharmacol. 69, 899-907.] also expressed M (3) and M (4) muscarinic receptors. Carbamylcholine, a mixed muscarinic/nicotinic receptor agonist, or oxotremorine M, a selective muscarinic agonist, elicited an elevation of cytoplasmic Ca (2+) concentration ([Ca (2+)](i)) and release of insulin. The maximal [Ca (2+)](i) response induced by carbamylcholine was larger than that of oxotremorine M or that of nicotine, suggesting that carbamylcholine enhanced the [Ca (2+)](i) response by stimulating two types of receptor. M (3) and M (4) muscarinic receptor antagonists inhibited the [Ca (2+)](i) responses to carbamylcholine and oxotremorine M, suggesting the involvement of these muscarinic receptors in the regulation of [Ca (2+)](i). In addition, pretreatment with carbamylcholine inhibited the [Ca (2+)](i) responses to oxotremorine M or nicotine, indicating that the effect of carbamylcholine on [Ca (2+)](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 A (2) (PLA (2)) inhibitor AACOCF (3) inhibited the [Ca (2+)](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. |
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