Glucocorticoid modification of the responsiveness of a fast (type 2) neuromuscular system to edrophonium and d-tubocurarine

The effects of an intensive triamcinolone diacetate pretreatment regimen in cats (8 mg/kg i.m. once daily/7 days) were examined on the facilitatory actions of edrophonium and the blocking effects of d-tubocurarine in a fast (type 2) neuromuscular system, the in vivo gastrocnemius-plantaris nerve-muscle preparation. In glucocorticoid-treated animals, i.v. edrophonium responsiveness, which was measured in terms of the potentiation of the indirectly evoked maximal muscle contractile tension, was significantly decreased compared with that in untreated cats. In contrast, the neuromuscular blocking potency of i.v. d-tubocurarine was reduced after triamcinolone treatment. Twice as much drug was required to achieve the same degree of reduction in indirectly evoked muscle tension. The decreased facilitatory potency of edrophonium was indicative of a glucocorticoid decrease in the excitability of type 2 motor neuron terminals. This was manifested as an attenuated ability to generate a stimulus-bound repetitive discharge in response to edrophonium and was the exact opposite of type 1 (soleus) motor axons which displayed an increased stimulus-bound repetitive discharge after treatment with a facilitatory drug as a result of intensive glucocorticoid action, reported previously. The decreased potency of d-tubocurarine, however, suggested an improvement in the evoked release of transmitter by single impulses and was in agreement with earlier work in soleus preparations. Taken together, the present data demonstrated the complexities of the direct effects of glucocorticoids on neuromuscular function.