Mobilization of cellular choline by stimulation of muscarine receptors in isolated chicken heart and rat cortex in vivo.
The effects of cholinesterase inhibitors and muscarinic agonists on efflux of choline were studied in isolated perfused chicken heart and rat cortex in vivo. In the heart, the phospholipase A2 inhibitor mepacrine (10(-4) M) reduced the choline efflux (1.1 nmol g-1 min-1) by 51 +/- 5% (N = 3), whereas several cholinesterase inhibitors (physostigmine, neostigmine and diisopropylfluorophosphate) and muscarinic agonists (acetylcholine, oxotremorine and bethanechol) caused an increase. The muscarinic increase in choline efflux appears to be specific, as the increase caused by 10(-6) M physostigmine (+113%), by 3 X 10(-7) M acetylcholine (+89%) or by 5 X 10(-4) M bethanechol (+29%) was blocked by atropine. Cholinesterase inhibitors and muscarinic agonists also caused a decrease in heart rate by about 50%. Papaverine (10(-5) M) blocked the physostigmine- or bethanechol-evoked increase in choline efflux, but left the decrease in heart rate unchanged. Choline efflux from rat cortex in vivo was studied using the "cup technique." During the experimental period (3 hr), resting efflux declined from 60 to 15 pmol cm-2 min-1. Again choline efflux was increased by physostigmine (+48%) or by bethanechol (+48%) added to the cup solution from 80 to 160 min, whereas a decrease was observed after atropine plus physostigmine (-36%) or atropine plus bethanechol (-26%). In conclusion, stimulation of muscarine receptors increased extracellular choline by mobilization of cellular choline presumably through an effect on phospholipid metabolism. The hypothesis is discussed that synthesis of acetylcholine in the brain may be supported by an autoregulation of precursor availability.
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D002645:Chickens; D002794:Choline / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010277:Parasympathomimetics / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D010277:Parasympathomimetics; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D001285:Atropine; D011796:Quinacrine; D002794:Choline; D000109:Acetylcholine