Presynaptic, facilitatory effects of the corticosteroid dexamethasone in rat diaphragm: modulation by beta-bungarotoxin.
Low concentrations of dexamethasone (up to 200 nM) increase the accumulation of choline (Ch) and its incorporation into acetylcholine (ACh) in the endplate rich area (EPA) of stimulated and unstimulated diaphragms in the presence of 10 microM Ch. Tissue ACh is not significantly altered, even after 140 min incubation. The specific radioactivity of the ACh in the EPA is thus increased by dexamethasone (Dex). The corticosteroid has no effects on acetylcholinesterase or choline acetyltransferase in diaphragm extracts. In the same medium, the amplitudes of the MEPPs, MEPCs and EPCs are also increased by Dex. Neither the quantal content of the EPCs nor the MEPP frequency, nor the half decay time of the MEPCs are altered. Therefore Dex (200 nM) increases both the resting and evoked output, and turnover of ACh in rat diaphragm. Beta-bungarotoxin (beta-BuTx) antagonizes the Dex-induced increase in Ch accumulation and its incorporation into ACh, and abolishes the increases in MEPC- and EPC-amplitudes, providing further argument for a presynaptic effect of Dex. In continuously-stimulated diaphragms, beta-BuTx causes an accumulation of ACh which is much greater than in unstimulated tissue. This accumulation of ACh is less in the presence of Dex, provided that Dex is added before beta-BuTx. The interaction of Dex and beta-BuTx is discussed in terms of their possible presynaptic sites of action.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D003964:Diaphragm / Q000294:innervation; D004558:Electric Stimulation; D005260:Female; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D009469:Neuromuscular Junction / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000502:physiology*
D002038:Bungarotoxins; D003907:Dexamethasone; D002794:Choline; D000109:Acetylcholine