FURTHER STUDIES ON INTRAVENOUSLY INJECTED CHOLINESTERASE PREPARATIONS

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

Pharmacological responses to acetylcholine (ACh), methacholine (MCh), and benzoylcholine (BCh), and to faradic stimulation of cardiac vagus and of cervical sympathetic were tested in dogs, cats and rats prior to and after intravenous administration of purified bovine erythrocyte acetylcholinesterase (AChE) and pseudocholinesterase (ChE, plasma fraction IV 6-3).

AChE (2,000 to 10,000 units) proved effective in blocking both the muscarinic and nicotinic responses to ACh but not to MCh and BCh. This block was transient (up to 30 minutes).

Even 60,000 units of AChE in rats failed to affect the slowing of the heart following peripheral vagus stimulation. In dogs, AChE was ineffective in blocking the physiological responses to stimulation of the cervical sympathetic (central end of the vago-sympathetic trunk) and of cardiac vagus.

ChE (2,000 to 12,500 units) proved effective in blocking for sometimes 20 hours both the vasodepressor and nicotinic effects of BCh, but did not affect the response to ACh and to MCh. It had no demonstrable effect on cholinergic nerve stimulation.

Injected ChE and AChE can be recovered from the plasma and, in small amounts, from smooth muscle. They cannot be recovered from sympathetic ganglia, brain and erythrocytes. Increased ChE activity in blood can be demonstrated for more than 20 hours (with 6,000 units dose).

ACh is hydrolyzed rapidly in drawn blood (both plasma and red blood cells) and AChE solutions. Mixtures of AChE and ChE do not hydrolyze ACh any faster than corresponding amounts of AChE alone.

The analysis of the above data offers suggestions as to the role of cholinesterases in circulating fluids ("transport" cholinesterases). AChE and not ChE component of "transport" cholinesterases is essential in hydrolysis of injected ACh; the ChE component is, however, active in hydrolysis of injected BCh.

The demonstration that injected ChE terminates pharmacological effects of BCh but not of ACh is in keeping with the earlier data showing that inhibition of ChE by small doses of DFP potentiates pharmacological effects of BCh but not of ACh.