The distribution in the rabbit of choline administered by injection or infusion

Abstract

SUMMARY1. The concentration of choline in plasma, erythrocytes, skeletal muscle, heart, lung, liver, small intestine and kidneys and the changes that follow the injection or infusion of choline have been measured in rabbits anaesthetized with pentobarbitone.2. The concentration of choline in the plasma of arterial blood was 11-8 + 0*6 n-mole/ml. and in the erythrocytes 28*4 + 1-3 n-mole/ml. blood.3. All tissues contained a higher concentration of free choline than did plasma. The values range from 19 1 + 2-2 n-mole/g in skeletal muscle to 500 + 25 n-mole/g in the kidney.4. In order of their choline concentrations the tissues were intestine (duodenal end) > kidney > intestine (caecal end) > liver > lung > brain > heart > erythrocytes > (blood) > skeletal muscle > plasma, while in order of the contribution to the total body choline they were liver > intestine > skeletal muscle > (blood) > kidney > erythrocytes > lung > brain > plasma > heart. The total free choline determined by these analyses was between 30-40 ,umole/kg body weight, about one third being present in the liver.5. The choline content of the small intestine varied along its length. The lowest amount being present in the portion adjoining the caecum.6. Within 1 min of the injection of choline 100 or 300 /Zmole/kg, 70-90 % had left the circulation. The proportionate loss was higher after 100 smole/ kg than after 300 /zmole/kg.7. The loss following 300 /zmole/kg was increased if that dose were preceded by a dose of 100 /tmole/kg 40 min earlier; this suggests some additional disposal mechanisms) had been activated by the first dose.8. Three minutes after the injection of choline 300 ,Lmole/kg, about 60 % was present as free choline in the tissues studied. The order of the J. E. GARDINER AND M. C. E. GWEE concentration increases was kidneys > liver > muscle > lung > small intestine (caecal end) > heart > intestine > small intestine (duodenal end) > brain.9. Forty minutes after the injection of choline 300 ,ltmole/kg, only 11 % could be accounted for as free choline. Only the levels in the kidney, liver, muscle and lung were significantly above normal at this time.10. Infusion of choline 0-8 jtmole/kg. min or greater produced rises in plasma choline that corresponded to a clearance of 32 ml. plasma/kg. min.11. After the infusion of 300 ,umole/kg over a period of 1 hr, raised levels of choline were detected in all tissues assayed, but the amount found accounted for only 14 % of the choline administered. The concentrations in the kidney, liver and lung were similar to those found 40 min after the injection of 300 /tmole/kg.12. There was no change in the concentration of choline in the erythrocytes after the injection of choline 100 or 300 jtmole/kg, nor during the infusion of choline at the rate of 5 /,tmole/kg. min for 1 hr.13. The plasma volume appeared to be affected by the injection of the large doses of choline; after choline 300 ,umole/kg the plasma volume was reduced. No effect on the plasma volume was observed during the infusion of the same dose.

Effect of Two Hemicholiniums on the Disposition and Distribution of Endogenous Free Choline in Anaesthetized Rabbits

“…The choline concentration of the brain, intestine, skeletal muscle or heart was not appreciably (Gardiner & Gwee, 1974) Ansell & Spanner, 1971). The rise in the choline concentration of the liver caused by TPHC-3 is puzzling.…”

“…The concentrations of choline in muscle, heart, brain and the terminal portion of the small intestine were unaffected by the administration of either hemicholinium. The choline concentrations in the control rabbits were reported previously (Gardiner & Gwee, 1974 Gardiner (1975) further showed that the rises following (+)-tubocurarine of TPHC-3 were prevented if the animals were artificially resuscitated.…”

“…The plasma choline concentrations were measured every 5 minutes. In other experiments, in the absence of a hemicholinium compound, it was observed that the rate of the choline infusion had to be larger than 400 nmol kg-' min-' to cause a significant rise in the plasma choline con- (ii) centration (Gardiner & Gwee, 1974). In the present experiments therefore choline was infused at rates of 200, 400, 800 and 1200 nmol kg-' min' for 15 min each.…”

“…In HC-3-treated animals the plasma choline concentration started to rise during the infusion of choline 200 nmol kg-' min-' whereas infusion rates of greater than 400 nmol kg-' min-' were required in untreated animals (Gardiner & Gwee, 1974). It is probable therefore that the entry of free choline, from the diet and from sites of synthesis, into the circulation is normally well below a rate of 200 nmol kg-' min-' but that during hemicholinium-induced respiratory distress, the rate of entry of choline from tissues into the circulation exceeds 200 nmol kg-' min-'.…”

“…The animals were anaesthetized with sodium pentobarbitone (50 mg/kg i.v.). The preparation of the animals, general experimental and analytical procedures, and choline bioassay have been described previously (Gardiner & Gwee, 1974).…”