Injection Of Choline Research Articles

A possible cholinergic link in olivo-cochlear inhibition

Electrical stimulation of the crossed olivo-cochlear bundle (OCB) of the anesthetized cat produces an inhibition of sound-evoked VIII nerve action potentials. The OCB has been shown to contain acctylcholinesterase ( Churchill et al., 1956) and synaptic vesicles ( Engstroem, 1958). It was therefore suggested that the OCB exerted its inhibitory effect by neurohumoral means and that the neurohumor might be acetylcholine (ACh). Hemicholinium number 3 (HC-3) was employed in the present study as a means for testing the hypothesis that ACh is involved in OCB-induced inhibition. Cats anesthetized with pentobarbital and with left middle ear muscle tendons severed were employed. Sound-evoked potentials were recorded from the left cochlear round window. The crossed OCB was stimulated electrically. All experimental drugs were injected via a cannula in the left axillary artery. Atropine (0.5–5 mg/kg), dihydro-β-erythroidine (2–10 mg/kg) and mecamylamine (2–5 mg/kg) infections did not antagonize OCB-induced inhibition. HC-3 (5 mg/kg) in the majority of cats reduced the OCB-induced inhibition. Choline injections and resting the preparation momentarily reversed the effect of HC-3. Under similar conditions, d-tubocurarine (2 mg/kg) produced no change in OCB-induccd inhibition.

Synthesis of acetylcholine from labeled choline by brain.

Abstract Choline-methyl-H 3 was employed in experiments in the cat in an attempt to label cerebral cortical stores of acetylcholine. Both Chromatographic and isotope dilution analysis established the presence and identity of labeled acetylcholine in extracts of unfractionated cerebral cortex as well as an undoubtedly crude mitochondrial fraction of this tissue after the intracerebral injection of tritium labeled choline. The radioactivity in this fraction was significantly reduced when hemicholinium No. 3 was injected into the cerebral cortex prior to the injection of tritiated eholine. The synthesis of labeled acetylcholine in the brain also was confirmed after intracerebral injection of tritiated choline in the young chick. The synthesis in vitro of tritiated acetylcholine from choline-methyl-H 3 by cerebral cortical homogenates of the cat was demonstrated. No synthesis of labeled acetylcholine could be detected when the homogenates were incubated with electric eel acetylcholinesterase. The possibility of nonenzymatic conversion of labeled choline to its acetyl ester in vivo seems highly unlikely since significant conversion did not occur in vitro under conditions that simulated those in vivo .

Severe agoraphobia: a controlled prospective trial of behaviour therapy.

Severe agoraphobia is difficult to treat. Encouraging immediate results have been reported with diverse treatments, including intensive psychotherapy (Friedman, 1959), acetyl choline injections (Sim, 1964), antidepressant drugs (King, 1962) and more recently with behaviour therapy (Wolpe, 1958). It is this latter claim which this paper examines. Early reports (e.g. Meyer, 1957; Wolpe, 1958) suggested that behaviour therapy might prove to be a rapid and effective treatment, but a small series studied by Meyer and Gelder (1963) demonstrated that results were not always as effective as single case reports suggested, and showed clearly that the treatment was often lengthy, taking 80 hours on the average. A retrospective investigation of a larger series (Marks and Gelder, 1965; Cooper, Gelder and Marks, 1965) again failed to support the early claims, although it was shown that behaviour therapy is an effective treatment for circumscribed phobias such as fears of animals and insects.

Study on relationship between effect of choline on respiratory quotient and adrenocortical function.

1) The influence of choline on the nonprotein respiratory quotient (R.Q.) was examined in the albino rats.2) The R.Q. in the 24-hour-fasted rats was 0.80, indicating that a significant amount of carbohydrate was still oxidized, whereas in the 48-hour-fasted rats the R.Q. was 0.71, indicating that fat was oxidized almost exclusively.3) When choline was injected to the 48-hour-fasted rats, protein catabolism was markedly depressed and the oxidation of fat was augmented.4) The administration of glucose raised the R.Q. to 0.90 in the 48-hourfasted rats. However, if these animals had received the injection of choline, the R.Q. was 0.68, indicating that the oxidation of carbohydrate was strongly inhibited and the oxidation of fat was augmented.5) The R.Q. in the 24-hour-fasted rats was 0.80 as described above, whereas that in the adrenalectomized or hypophysectomized rats was decreased to 0.72. It is evident from these results that the oxidation of carbohydrate was depressed in these animals.In consideration of the results obtained in the experiments by Okada6) and Nakata et al.7) which pointed out the inhibitory action of choline on the adrenocortical function, the inhibition of carbohydrate oxidation by the injection of choline as shown in the present experiment may be ascribed to the lowered adrenocortical function.6) Catabolism of protein in the 24-hour-fasted rats was decreased by the adrenalectomy and it was still decreased by the injection of choline.7) According to the above results, the injection of choline augments the oxidation of fat through its inhibitory action on the oxidation of carbohydrate and protein in the body. This effect of choline may be ascribed to the inhibition of the adrenocortical function. The data also indicated that choline inhibits the development of fatty livers without inhibiting the oxidation of fat as an energy source.The authors wish to express sincere thanks to Emeritus Professor Y. Sueyoshi for his unfailing guidance throughout the course of this work and in the preparation of this treatise.

Actions of triethylcholine on neuromuscular transmission.

The effects of the triethyl analogue of choline (triethyl 2-hydroxyethyl ammonium) on muscular activity have been studied in conscious rabbits, chicks, dogs and a cat. The contractions of the tibialis anticus and soleus muscles of cats under chloralose anaesthesia, and of the tibialis anticus muscle of rabbits under urethane anaesthesia and the isolated diaphragm preparation of the rat were also used. In conscious animals, triethylcholine caused a slowly developing muscular weakness which was more severe after exercise and which resembled the symptoms of myasthenia gravis. In nerve-muscle preparations triethylcholine had a selective action in reducing the contractions of muscles elicited by a high rate of nerve stimulation while leaving unaffected the contractions caused by slower rates of stimulation. During the paralysis of the tibialis muscle of the cat produced by triethylcholine, action potentials recorded from the motor nerve were unaffected and the muscle responded normally to injected acetylcholine and to direct electrical stimulation. The failure of neuromuscular transmission produced by triethylcholine was reversed by injection of choline, but anticholinesterases were ineffective. Choline reduced the toxicity of triethylcholine in mice. It is concluded that triethylcholine produces transmission failure at the neuromuscular junction by interfering with the ability of the nerve endings to synthesize acetylcholine. The possibility that triethylcholine is itself acetylated by the nerve endings and released as an inactive neurohormone is discussed. It was shown that triethylcholine was devoid of depolarizing action and curare-like blocking action. It possesses a transient ganglion blocking action of the tetraethylammonium-type as shown in experiments in which it caused a fall in blood pressure and blocked the response of the nictitating membrane to pre- but not to post-ganglionic stimulation of the cervical sympathetic nerve.

The effect of choline 2,6-dichloro phenyl ether bromide (TM-25) on organ content and urinary excretion of catecholamines.

AbstractDaily injections of choline 2,6‐dichloro phenyl ether bromide (TM‐25) in the rat greatly reduces the urinary output of noradrenaline and to a lesser extent that of adrenaline. After 5–6 days of treatment with TM‐25 the catecholamine content of adrenals, heart and spleen is considerably reduced. It is inferred from the results that TM‐25 interferes with the production, release or storage of catechol amines in the adrenergic nerves and possibly in the adrenals.

The effects of insulin, reserpine and choline 2:6-xylylether bromide on the adrenal medulla and on medullary autografts in the rat.

SUMMARY The adrenaline and noradrenaline content of the adrenal medulla and medullary implants has been assessed by histochemical and assay techniques after the injection of insulin, reserpine, and choline 2:6-xylylether bromide (TM10) into Wistar and Sprague-Dawley strain rats. Insulin hypoglycaemia is without effect on implanted chromaffin cells, but reduces the adrenaline content of the intact adrenal. Reserpine reduces the catechol amine content of both normal and grafted chromaffin cells. TM10, given as a single intravenous injection, has no effect on either normal or implanted chromaffin cells.

Effects of Choline on the Leucocyte Picture and on the Serum Cholinesterase Activity in Rabbits

In 1906, Werner and Lichtenberg reported that choline injections in rabbits produce sterility or lessened fertility, analogous to the effects of x-ray or thorium X, which was followed by Werner and Asher, reporting blood and skin changes similar to that produced by x-ray (1–4).

Effects of choline on the leucocyte picture and on the serum cholinesterase activity in rabbits.

In 1906, Werner and Lichtenberg reported that choline injections in rabbits produce sterility or lessened fertility, analogous to the effects of x-ray or thorium X, which was followed by Werner and Asher, reporting blood and skin changes similar to that produced by x-ray (1–4).

The effect of other lipotropic substances on the fate of choline after oral and intravenous administration.

1. In vitro degradation of choline to trimethylamine (TMA) by fecal bacteria is unchanged in the presence of methionine, inositol, or both. 2. Rats fed methionine and inositol together with choline excreted the same amount of TMA in the urine as rats fed choline alone. Human experiments duplicated the experience in animals. 3. Humans excrete the same amount of choline in the urine following the intravenous injection of methionine, inositol and choline together as they do following the injection of choline alone. 4. The intravenous injection of methionine, inositol, and choline in relatively large amounts is well tolerated and appears to be without danger. 5. The presence of the lipotropic agents methionine and inositol does not appear to influence the degradation or excretion of choline after oral or intravenous administration, again pointing to the differences in the lipotropic action of these substances. We wish to thank Dr. Hans Popper for this generous advice during the conduct of tliis investigation.

The contraction of the extrinsic muscles of the eye by choline and nicotine

It has long been known that choline, acetylcholine (Reisser, 1921), and nicotine (Langley, 1906-14) contract the normal striped muscle of Sauropsidæ (frog, fowl, etc.), and it has been recently demonstrated that a similar reaction occurs in the fœtal muscle of mammals (Rückert, 1930), but hitherto it has never been shown to occur in the muscles of the fully-developed mammalian. It has also been well established that the voluntary muscles of mammals, after degeneration of the motor nerves, exhibit a "pseudo-motor" contraction on the injection of choline. (Frank, Northmann and Hirsch-Kauffmann, 1922-23), a contraction which appears analogous in origin and in nature to that first described in the tongue by Vulpian and Phillipeaux (1863), and in the muscles of the limbs by Sherrington (1894), which occurs on stimulation of the sensory roots after the motor roots have degenerated. Recent writers in discussing the theoretical basis of these phenomena have stressed the point that this type of contraction occurs in mammals only after degeneration of the motor nerves, and have based some of their conclusions upon this assumption. The following experiments show, however, that this statement is no universally true, and that the extrinsic muscles of the eye form an exception to the general rule. The matter arose as a side-issue during an extended research on the mechanism controlling the intra-ocular pressure, when anomalous changes were noted while investigating the effect of choline and acetylcholine upon the pressure in the eye. These experiments are recorded in a separate publication (Duke-Elder, 1930): it is sufficient for the present purpose to say that in experiments upon anæthetised dogs, while small doses of choline such as produce a depressor effect when injected intra-venously (0·2 c. c. of a 1 in 20 solution) give rise to a fall in the intra-ocular pressure of the order which would be expected from the events in the vascular circulation, larger doses, on the other hand, lead to an increase in the intra-ocular pressure much larger than could be explained by any vascular events. In order, therefore, to reduce the number of variables with which we were dealing, the technique was extended to the perfusion of the eye with an artificial circulation, whereby the conditions in the general circulation were kept constant (Duke-Elder, 1930); and fig. 1 shows that in these circumstances, even when we would have expected a fall in the intra-ocular pressure owing to a local vasoconstriction when the pressor component of choline was elicited, a rise was obtained. The most significant feature was that this rise was accompanied by a movement of the base-line in the tracing registered by the optical manometer denoting a movement of the eye in the direction of enophthalmos.