Neostigmine augments responses of the rat anococcygeus muscle to field stimulation

1 The effects of neostigmine on noradrenergic transmission have been studied in the field stimulated, isolated anococcygeus muscle of the rat. 2 In those muscles where the excitatory response to field stimulation was not completely inhibited by guanethidine (5 × 10 −6 to 10 −5 m ) or phentolamine (10 −6 m ), atropine (5 × 10 −8 m ) gave no further inhibition of the response. 3 The shape of the response to field stimulation was altered in a dose‐dependent manner by neostigmine (5 × 10 −7 to 5 × 10 −6 m ), such that a ‘shoulder’ appeared during the relaxation phase. The ‘shoulder’, present at all stimulation frequencies tested between 3 and 40 Hz, was abolished by atropine (5 × 10 −8 M) and unaffected by tubocurarine (10 −6 m ). 4 Neostigmine (2.5 × 10 −6 m ), whether alone or in the presence of atropine (5 × 10 −8 m ), had no effect on the uptake or stimulation‐induced release of [ 3 H]‐noradrenaline. 5 Using electron microscopy, small Schwann/axon bundles close to smooth muscle cells rarely showed Cholinesterase staining, whereas larger bundles at the outer serosal aspects of the muscle exhibited dense staining. 6 It is concluded that the observed effects of neostigmine are not due to a presynaptic effect on noradrenergic transmission.