Phosphoinositide metabolism and cGMP levels are not coupled to the muscarinic-cholinergic receptor in human erythrocyte.
Recently, Tang et al. [BBA 772, 235 (1984)] reported that cholinergic agonists stimulate calcium uptake and cGMP formation in the human erythrocyte. We undertook this investigation since polyphosphoinositide breakdown precedes calcium mobilization and cGMP formation in several tissues. In [32P]-prelabeled erythrocyte ghosts, calcium (0.5 mM) but not carbachol (0.1 mM) caused a 2- and 20-fold increase in the accumulation of IP2 and IP3, respectively. This was accompanied by a 50% decrease in PIP2 and PIP. In intact erythrocytes prelabeled with [32P], 1 microM A23187 but not carbachol (0.1 mM) produced a 300% increase in radioactivity in PA after a 30-min incubation. cGMP levels after a 2-min incubation with saline, A23187 (1 microM), or carbachol (0.1 mM) were 0.27 +/- .03, 0.27 +/- .04, and 0.34 +/- .04 fmol/10(6) cells. Our studies indicate that the muscarinic receptor in the erythrocytes is "non-functional" insofar as its stimulation is not accompanied by phosphoinositide breakdown or cGMP formation.
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis*; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D000001:Calcimycin; D002217:Carbachol; D006152:Cyclic GMP; D002118:Calcium