ISSN:
1432-1912
Keywords:
Key words SK&F 96365
;
M3 muscarinic receptor
;
Phosphoinositide turnover
;
SH-SY5Y neuroblastoma
;
Cerebellar granule cells
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract SK&F 96365, a receptor-mediated Ca2+ entry inhibitor, has been reported to inhibit Ca2+ res- ponses to various agonists without affecting internal Ca2+ release and phosphoinositide turnover. Since muscarinic acetylcholine receptor-mediated phospho- inositide turnover shows a marked dependence on factors affecting cytosolic Ca2+ concentration, the effects of SK&F 96365 on the coupling of muscarinic receptors to the phosphoinositide hydrolysis were examined in human neuroblastoma SH-SY5Y and rat cerebellar granule cells. SK&F 96365 concentration-dependently (3–30 μM) inhibited the inositol phosphate formation elicited by carbachol in both cellular systems. Moreover, SK&F 96365 inhibited the carbachol-induced inositol phosphate formation in the absence of extracellular Ca2+, and similar extent of inhibition was achieved in the presence or absence of extracellular Ca2+. In ligand binding studies, we found that the binding affinities for [3H] N-methyl scopolamine in both cells were attenuated by SK&F 96365 (3–30 μM), while Bmax values for the ligand were not changed. The competition curves of SK&F 96365 showed a Ki value of 28.4 uM in SH-SY5Y cells. The results indicated that the decrease of carbachol-stimulated phosphoinositide hydrolysis by SK&F 96365 is due to the competitive inhibition of agonist binding to the M3 muscarinic receptors.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00168706
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