McHardy Smith - Muscarinic cholinergic receptors of two cell lines that regulate cyclic AMP metabolism by different molecular mechanisms.

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  Evans, T, Smith, MM, Tanner, LI, Harden, TK 26 395-404-

  Abstract: The attenuation of cyclic AMP   accumulation occurs by different mechanisms in 1321N1 astrocytoma   cells and NG108-15 neuroblastoma X glioma cells. In 1321N1 cells,   cholinergic agonists reduce cyclic AMP accumulation through a   Ca2+-dependent activation of phosphodiesterase; in NG108-15   cells, muscarinic receptor-mediated effects on cyclic AMP   metabolism occur through inhibition of adenylate cyclase. The   goal of the current study was to determine whether different   pharmacological specificities were expressed by the muscarinic   receptor populations of these two cell lines. The affinity of   muscarinic receptors for [3H]quinuclidinyl benzilate (6 pM),   [3H]N-methylscopolamine (50 pM), and atropine (80 pM) was similar   in membrane preparations from each cell line. The affinity of the   antagonist, pirenzepine, which has been proposed to be a   selective ligand for a muscarinic receptor subtype, was 3-fold   higher in competition binding assays carried out with membranes   of 1321N1 cells, than with NG108-15 cells. The Hill coefficients   of pirenzepine competition curves were not significantly   different from unity in both cell lines. This selectivity of   pirenzepine was also apparent in studies of the competitive   inhibition of carbachol-induced attenuation of cyclic AMP   accumulation in intact cells. Differences in the relative   affinities of agonists were observed in competition binding   analyses carried out with membranes in the presence of GTP and   absence of Mg2+. The Ki values of bethanechol and carbachol were   5- and 12-fold lower for receptors of NG108-15 cells than those   of 1321N1 cells and the Ki of methacholine was 3.5-fold lower for   1321N1 cells than for NG108-15 cells. The affinities of   oxotremorine and arecoline were similar between the two cell   lines. These differences in agonist affinities between the two   cell lines were much smaller in analyses of muscarinic   receptor-mediated effects on cyclic AMP metabolism in intact   cells. Taken together, these data suggest that muscarinic   receptors of differing pharmacological specificities regulate   cyclic AMP metabolism by different mechanisms in 1321N1 and   NG108-15 cells.

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