Decreased cAMP levels in human diploid cells exposed to cholinergic stimuli.
Carbachol at a concentration of 1 micron caused very significant decreases in PGE1 stimulated cAMP levels in three human diploid lung fibroblasts, WI-38, MRC-5, and IMR-90. Detailed studies with WI-38 cells showed that carbachol acted at low concentrations and very rapidly, cAMP levels being reduced by 50% in about 1 minute. The effect was moderately reduced but still very significant in Ca++ free medium containing 10(-5)M EGTA. Acetylcholine (in the presence of physostigmine), pilocarpine, and muscarine lowered cAMP levels at concentrations of 1 or 10 micron. The effects of carbachol were exquisitely sensitive to atropine but were unaffected by hexomethonium or d-tubocurarine. These data suggested that the cholinergic response of WI-38 cells was of the muscarinic type.
D000109:Acetylcholine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006801:Humans; D009116:Muscarine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
D006584:Hexamethonium Compounds; D010277:Parasympathomimetics; D011458:Prostaglandins E; D010862:Pilocarpine; D001285:Atropine; D009116:Muscarine; D002217:Carbachol; D010830:Physostigmine; D000242:Cyclic AMP; D000109:Acetylcholine; D002118:Calcium; D014403:Tubocurarine