Muscarinic activation of phosphatidylinositol breakdown in neuroblastoma cells

RESUMO

Hydrolisis of phosphatidylinositol (PtdIns) has been shown to occur as a consequence of muscarinic activation in pancreas and salivary glands and has thus been proposed as a step in the sequence of muscarinic activation in general. Since a role of such a mechanism in the central nervous system has not been determined, neuroblastoma cells in culture were used in the present investigation to explore the relationship between phosphoinositide metabolism and muscarinic receptor activation. It was found that 10-3 M and 10-8 M carbachol causes a decrease in the amount of label associated with [3H] phosphatidylinositol within 30 seconds. Furthermore, 10-5 M atropine sulfate selectively blocks this response, indicating the muscarinic nature of the effect. These results suggest that phosphatidylinositol metabolism could be an early step in muscarinic receptor activation and that neuroblastoma cells provide a suitable model to study the biochemical mechanism of cellular activation by muscarinic receptors in the central nervous system