The effects of 6-azauridine on the peripheral nervous system—I. The action on ganglionic transmission

The action on ganglionic transmission of 6-azauridine, an antimetabolite of pyrimidine nucleotides, was studied in the sympathetic superior cervical ganglion of the cat. The action potential evoked by preganglionic stimulation and asynchronous discharge caused by close intra-arterial injections of acetylcholine were recorded from postganglionic fibers. The administration of low doses of 6-azauridine (50–70 μg) resulted in an increase in action potential amplitude and in prolongation of the asynchronous discharge. Medium doses (200–500 μg), caused an initial decrease in amplitude of both the action potential and asynchronous discharge, followed by a delayed increase in action potential amplitude and prolongation of the asynchronous discharge. After the administration of higher doses (1–5 mg) preganglionic stimulation or acetylcholine administration failed for several hours to evoke any response. After administration of low and medium doses of 6-azauridine, hexamethonium (0·5–2·0 mg) ord-tubocurarine(0·4 mg) completely blocked the prolonged asynchronous discharge. However, atropine (1–2 μg) caused the disappearance of the prolongation of asynchronous discharge alone. Tetanic stimulation and physostigmine administration were not capable of restoring the responses blocked by high doses of 6-azauridine. It is suggested that the facilitatory action of 6-azauridine might be due to an unmasking of muscarinic cholinergic receptors in the ganglion. The inhibitory effects might be due to the blocking of nicotinic receptors alone after administration of medium doses, and to the blocking of both nicotinic and muscarinic receptors after the administration of high doses of 6-azauridine.