Irreversible inhibition of phospholipid methylation and protein carboxymethylation does not alter acetylcholine receptor function in muscle cells.
The role of methyltransferase (MT) reactions in acetylcholine (ACh)-evoked depolarization and contraction in primary chick myotubes was determined by using a mixture of erythro-9-(2-hydroxy-3-nonyl) adenine, homocysteine thiolactone, and adenosine which together inhibit the activity of MT. Carboxy-MT and lipid-MT activities were inhibited irreversibly by 91 and 100%, respectively. ACh-induced muscle contraction was also inhibited within 10 min after application of the inhibitor mixture. However, in contrast to permanent inhibition of MT activities, inhibition of acetylcholine receptor (AChR)-dependent muscle contraction was reversible. Moreover, physiological studies showed that the inhibitor mixture had no effect on resting membrane potential or ACh-induced depolarization or desensitization. These results suggest that AChR function is not altered by methylation inhibitors and that changes in AChR-mediated contraction are not due to inhibition of MT activities.
D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D004553:Electric Conductivity; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010743:Phospholipids / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000502:physiology*
D009124:Muscle Proteins; D010743:Phospholipids; D011950:Receptors, Cholinergic; D008780:Methyltransferases; D002262:Carboxy-Lyases; D000109:Acetylcholine