Neosurugatoxin: CNS acetylcholine receptors and luteinizing hormone secretion in ovariectomized rats

Abstract

Neosurugatoxin, a neurotoxin isolated from the Japanese ivory shell, inhibits ganglionic nicotinic acetylcholine receptors but not skeletal muscle nicotinic acetylcholine receptors. It has also been reported to inhibit (3H) L-nicotine binding to high-affinity agonist acetylcholine receptors in rat brain membrane preparations. In the present study, 10(-5) M neosurugatoxin inhibited the in vitro binding of (3H) L-nicotine to the medial habenular nucleus of frozen, coronal sections of rat brain as did 10(-5) M cytisine or nicotine and 10(-4) M dihydro-beta-erythroidine. Neosurugatoxin did not inhibit (125I) alpha-bungarotoxin binding to hypothalamic synaptosomal preparations or to frozen, coronal sections of rat brain. Injection of neosurugatoxin into the third ventricles of ovariectomized rats resulted in a significant decrease in the frequency of pulses of luteinizing hormone (LH) secretion but had no effect on the amplitude of pulses. A low dose (1 microgram/injection) of the nicotinic acetylcholine agent cytisine injected into the third ventricle had no significant effect on pulsatile LH secretion. Coadministration of cytisine could block the inhibitory effect of neosurugatoxin on LH secretion. It is suggested that neosurugatoxin is a useful antagonist to study the biological roles of a specific subclass of nicotinic acetylcholine receptors in mammalian brain and reproductive neuroendocrine functions.