Possible Interaction: Carbachol and Phosphatidylinositol 4,5-Diphosphate

“In contrast, PLC activities, measured with exogenous phosphatidylinositol-4,5-bisphosphate [Ptdns(4,5)P2] in HEK cell lysates, were not altered, suggesting that carbachol pretreatment may enhance the cellular level of Ptdlns(4,5)P2.”

“PtdIns3P is metabolically closely related to the pool(s) of inositol phospholipid(s) that serves as substrate(s) for an agonist-sensitive phosphoinositidase C, as the levels of PtdIns3P fell significantly when 1321 N1 cells were stimulated with carbachol.”

“ CCh stimulated not only PI-PLC (G-protein-mediated) but also, by an as yet … ratio, by 100%, and further increased the flux from PI to PIP and PIP2 , GTP gamma S and NaF mimicked the effects of CCh … and PIP2, TPA raised the PIP:PI ratio by 75%.”

“ Carbamoylcholine (1 mM)added together with GTPγS increased the extent of PIP2 hydrolysis over that elicited by GTPγ increased the extent of PIP2 hydrolysis over that elicited by GTPγS alone and this stimulation was blocked by the muscarinic receptor antagonist, atropine (50 μM).”

“However, when added together, CCh and GTP gamma S increased PIP2 hydrolysis by 46%.”

“In the guinea pig myometrium, carbachol , oxytocin, and fluoroaluminates stimulated the breakdown of phosphatidylinositol 4,5-bisphosphate , which was insensitive to pertussis toxin [Biochem.”

“The muscarinic agonist, carbachol , stimulated PIP2 hydrolysis and the generation of IP 3 to five-fold the control levels.”

“ Carbachol stimulated [3H]phosphatidylinositol 4,5-bisphosphate ( PIP2 ) breakdown was inhibited by atropine and guanosine 5'-O-(2-thiobisphosphate).”

“After preincubation with 32P-orthophosphates, carbachol also evoked a rapid decrease in 32P-labeling of phosphatidylinositol-4,5-bisphophate with concomitant increase in 32P-labeling of phosphatidic acid.”

“Stimulation of muscarinic receptor by carbachol (1 mM) resulted in a decrease in 32Pi incorporation into phosphatidylinositol-4,5-bisphophaphate (TPI) and phosphatidylinositol-4-phosphate (DPI), and an increase in 32Pi incorporation into phosphatidylinositol (PI) and phosphatidic acid (PA), whereas no significant effect on other membrane phospholipids was found.”