Acetylcholine stores in rat diaphragm are increased by higher concentrations of dexamethasone.
In indirectly stimulated hemidiaphragms, dexamethasone (Dex, 2 microM) causes a significant increase in tissue acetylcholine (ACh) content. No increase in tissue ACh is found with 0.2, 0.6 or 6 microM Dex. Physostigmine (Physo, 15 microM) also causes an increase in tissue ACh, which is even greater in the presence of Dex (6-25 microM). There is no increase in ACh due to Dex, with 50 microM Dex plus Physo. The order of addition is important, as the Dex-induced increase in ACh is only found when Dex is added before Physo. No increase in twitch tension is found with any of these treatments. No Dex-induced increase in ACh is found with unstimulated hemidiaphragms. Similar increases in ACh are also found with other glucocorticoids (plus Physo), namely prednisolone (6-9 microM), corticosterone (2 microM) and hydrocortisone (2 microM). The mineralocorticoid aldosterone (2 microM), and other types of steroids cause no increase in tissue ACh. The increases in hemidiaphragm ACh are not found in a Na+-depleted medium, or in a medium containing 20 mM Mg2+ extra. The increase in ACh due to Physo is Ca2+-dependent, even though an increase in ACh due to Dex plus Physo is found in the absence of Ca2+. No increase in ACh due to either Physo, or Dex plus Physo are found in the presence of the nicotinic antagonists (+)-tubocurarine (5 microM) or alpha-cobrotoxin (5 micrograms/ml), while the muscarinic ligands atropine or oxotremorine (10 microM) abolish the extra increase in ACh due to Dex.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D013256:Steroids / Q000494:pharmacology
D013256:Steroids; D003907:Dexamethasone; D010830:Physostigmine; D000109:Acetylcholine