The Action of Nicotine on the Motor Endplate in the Cat

Abstract

Although nicotine gives its name to one of the principal actions of acetylcholine-the " nicotinic" action on skeletal muscle-the effects of nicotine on mammalian muscle (as distinct from amphibian or avian muscle) have been studied relatively rarely. The most recent analysis was that by Bacq & Brown (1937) who showed that arterial injections of nicotine into the gastrocnemius of the cat produced a contraction of the muscle followed by a prolonged depression of the response to nerve stimulation. They also noted that repetitive stimulation of the nerve relieved the depression of the twitch. There is no information, however, which allows a confident comparison between the effects produced by nicotine and those produced by, for instance, decamethonium or d-tubocurarine. The experiments described here analyse, on cat muscle, some of the characteristics of the action of nicotine in the light of recent knowledge. METHODSCats anaesthetized with chloralose after induction by ethyl chloride and ether were used in all experiments. A tracheal cannula was inserted, and a venous cannula in either the femoral or jugular vein. For injecting into the iliac artery of one leg, the opposite iliac artery and the descending pelvic artery were ligated and a Gordh needle was inserted into the ligated iliac artery pointing centrally so that injections were carried into the open artery on the other side. Some minutes after each injection, an injection of saline 0.5 ml. was made to wash out the needle and arterial deadspace. The contractions of tibialis, soleus or gastrocnemius were recorded using a flat spring myograph writing with a light lever on a smoked drum. The sciatic nerve in the thigh was tied close to the hip; shielded platinum stimulating electrodes were placed on it during its course through the hamstrings. For stimuli, square wave maximal shocks of 0.5 msec duration were used. For close arterial injections into the tibialis muscle, the technique of Brown (1938) was followed.

The effect of neosurugatoxin on the release of neurohypophysial hormones by nicotine, hypotension and an osmotic stimulus in the rat

“…nicotine has been shown to release vasopressin alone (Bisset et al, 1975;Bisset & Feldberg, 1977). Many of the actions of nicotine, including the release of vasopressin, exhibit tacahyphylaxis (Paton & Savini, 1968 Figure 9 Results of two series of experiments in water-loaded rats under ethanol anaesthesia in which two i.v. injections (SNI and SN2; n = 8) of 200 glg sodium nitroprusside, or two i.c.v.…”

Discrimination between nicotinic receptors in vertebrate ganglia and skeletal muscle by alpha‐bungarotoxin and cobra venoms.

“…Receptors for acetylcholine (ACh) were classified by Dale (1937 a) as nicotinic or muscarinic by analogy to the action of the alkaloids nicotine or muscarine (Dale, 1937a, b). Nicotine in low doses activat ines and higher doses blocks transmission both at autonomic ganglia and at the skeletal neuromuscular junction (Langley & Magnus, 1905;Bacq & Brown, 1937;Paton & Savini, 1968). The receptors mediating these responses to nicotine and to ACh are classically 'nicotinic'.…”

“…Even nicotine differs in the details of its action at the two sites. At the skeletal neuromuscular junction the action of nicotine is predominantly stimulant and the drug seems to lack the intense and prolonged phase of selfantagonizing block characteristic of its action on ganglia (Paton & Savini, 1968). These differences between the action of drugs at nicotinic receptors in the two locations could be explained if the receptors are not, as their classification implies, the same.…”

The effect of chronic nicotine and withdrawal on intra-axonal transport of acetylcholine and related enzymes in sciatic nerve of the rat

“…Nicotine is effecting not only the ganglionic transmission, but also the neuromuscular end-plate (cf. Paton and Savini, 1968) but in this study we did not measure the ACh turnover in the ske!etal muscle of these rats. However, it is possible that the activity of the motor neuron is changed a~er nicotine chronically and in particular after withdrawal.…”

“…Paton and Savini, 1968;Volle and Koelle, 1970). Thus, there are several observations that indicate that the peripheral motor neuron may be influenced by nicotine in a number of ways; (a) an increased turnover of NA in nerve terminals of bulbo-spinal NA neurons, ending close to the motor somata in the gray matter of the spinal cord (DahlstriSrn and Fuxe, 1965), may influence the motor neuron, (b) a release of ACh from vesicles or end-plates may occur also in the peripheral motor neuron, and (c) nicotine influences transmission at the motor end-plate.…”