The generation of nerve and muscle repetivie activity in the rat phrenic nerve-diaphragm preparation following inhibition of cholinesterase by ecothiopate. (1/3)

1 Simultaneous extracellular recordings were made from two end-plate zones of the isolated diaphragm and from the phrenic nerve of the rat in response to stimulation of the nerve. The contractions of the diaphragm were also recorded.2 In the curarized diaphragm, the introduction of ecothiopate, a non-competitive inhibitor of cholinesterase, caused a threefold increase in the amplitude of the end-plate current and an eightfold increase in the duration at half the peak amplitude.3 In the non-curarized diaphragm, the introduction of ecothiopate caused the generation of repetitive activity (RA) in first the phrenic nerve: this was then followed by RA in the diaphragm. At that stage, nerve RA possessed a shorter latency than muscle RA. The generation time for nerve RA was 1.6 ms and for mRA, it was 2.7 milliseconds.4 Nerve RA was more labile than muscle RA; it was readily abolished by increasing the frequency of stimulation, by magnesium, by tubocurarine or by high concentrations of ecothiopate, whereas muscle RA was still generated. Steady exposure to acetylcholine abolished both forms of RA.5 Two competitive inhibitors of cholinesterase, neostigmine and ambenonium, were also shown to evoke RA in nerve and muscle. The generation times for nerve RA and muscle RA were similar to those following ecothiopate.6 It was concluded that nerve RA and muscle RA were generated after the inhibition of cholinesterase by ecothiopate as a result of the prolonged action of acetylcholine upon cholinoceptive sites on the nerve terminal and motor endplate respectively. A direct excitatory action of ecothiopate upon the phrenic nerve terminals was excluded.  (+info)

Thymoma, myasthenia gravis, erythroblastopenic anemia and systemic lupus erythematosus in one patient. (2/3)

A 50-year-old woman who initially had myasthenia gravis subsequently presented with thymoma, erythroblastopenic anemia and systemic lupus erythematosus during 17 years of follow-up. In a review of the literature no similar documented cases were found, although 14 patients were reported with three of the above diseases, two also having positive LE cell tests. An association of several autoimmune disorders in one patient may be more frequent than was previously believed.  (+info)

The synthesis, turnover and release of surplus acetylcholine in a sympathetic ganglion. (3/3)

1. Surplus acetylcholine (ACh) is the extra ACh that accumulates in cholinergic nerve endings when they are exposed to an anticholinesterase agent. The synthesis and turnover of this ACh was examined in the cat's superior cervical ganglion.2. Surplus ACh did not accumulate in chronically decentralized ganglia perfused with eserine-choline-Locke solution, and this shows that it is stored in presynaptic nerve terminals.3. Surplus ACh accumulated more rapidly in ganglia perfused with eserine than in ganglia perfused with neostigmine or with ambenonium; accumulation was delayed by 45-60 min when a quaternary anticholinesterase was used. However, the release of ACh upon preganglionic nerve stimulation was the same during perfusion with eserine, neostigmine or ambenonium. It is concluded that intracellular acetylcholinesterase normally destroys surplus ACh, whereas extracellular enzyme destroys released ACh.4. When ganglia were perfused with [(3)H]choline and eserine, the surplus ACh that accumulated was labelled but its specific radioactivity was only 38% of that of the choline added to the perfusion fluid.5. Surplus ACh was not released by nerve stimulation and was not mobilized for release during, or after, prolonged nerve stimulation. It is concluded that ACh released by nerve impulses is replaced by synthesis at the site of ACh storage and not by movement of ACh from the surplus pool.6. The accumulation of surplus ACh no more than doubled the total ACh content of ganglia, but turnover of ACh continued when the total amount was constant. Surplus ACh may contribute to spontaneous ACh output from eserinized preparations.7. When ganglia were perfused with a medium containing high K(+) (56 mM), surplus ACh was released.  (+info)