STUDIES ON INTRAVENOUSLY INJECTED TRUE CHOLINESTERASE

¹ Department of Pharmacology and Materia Medica, Georgetown University School of Medicine, Washington 7, D. C.

Intravenous administration of from 2,000 to 5,000 units per kgm. of purified bovine erythrocyte (true) cholinesterase (ChE) causes, in anesthetized, non-atropinized dogs and cats occasional falls of blood pressure and respiratory difficulties. Atropine appears to protect to a large extent against these effects.

Bovine erythrocyte ChE (2,000 to 5,000 units per kgm.) abolishes in cats and dogs (15 to 30 minutes) the muscarinic and nicotinic effects of acetylcholine and the muscarinic effects in turtles. It does not prevent the pressor effects due to ganglionic stimulation by nicotine and by faradic stimulation of the cervical sympathetics in dogs and cats, or the cardiac slowing due to faradic stimulation of the peripheral vagus (5,000 units of ChE in dogs and cats and up to 30,000 units in turtles). However, physostigmine bradycardia in turtles was abolished by ChE.

In animals in which abdominal organs (particularly the liver) are excluded from circulation, the anti-acetylcholine effects of ChE are prolonged up to five times.

In cats, five minutes following the administration of 5,000 units per kgm. of ChE it can be recovered quantitatively from plasma; no additional ChE could be found, however, in red blood cells and sympathetic ganglia. Although ChE added to drawn blood remains active for at least 48 hours, in vivo the increased ChE activity in the plasma lasts only for 20 to 30 minutes. Subsequently, subnormal levels of ChE activity are frequently recorded.

The anti-acetylcholine effects of injected ChE may be explained by the increase of ChE in plasma. This ChE contributes then to the activity of the "transport" (circulating) ChE which hydrolyzes acetylcholine before it reaches the neuroeffectors. Since the injected ChE could not be recovered from the ganglia and the red blood cells, its failure to affect ganglionic and vagus stimulation by agents other than acetylcholine may be entirely or partially due to its inability to reach the strategic neuroeffectors.