Choline, CDP-choline or phosphocholine increases plasma glucagon in rats: Involvement of the peripheral autonomic nervous system

The present study was designed to test the effects of choline, cytidine-5′-diphosphocholine (CDP-choline) and phosphocholine on plasma glucagon concentrations in rats. Intraperitoneal (i.p.) injection of 200–600 μmol/kg of choline, CDP-choline or phosphocholine produced a dose-dependent increase in plasma glucagon and choline concentrations. Pretreatment with hexamethonium (15 mg/kg; i.p.), a peripherally-acting ganglionic nicotinic acetylcholine receptor antagonist, entirely blocked the increases in plasma glucagon by 600 μmol/kg of choline, CDP-choline or phosphocholine. The increases in plasma glucagon by these choline compounds was reduced significantly (P < 0.01) by about 25% by pretreatment with atropine methylnitrate (2 mg/kg), a peripherally-acting muscarinic acetylcholine receptor antagonist. Blockade of central acetylcholine receptors did not alter the increase in plasma glucagon induced by i.p. choline (600 μmol/kg). While α2-adrenoceptor blockade or bilateral adrenalectomy attenuated the increase in plasma glucagon evoked by choline compounds, blockade of α1- or β-adrenoceptors or chemical sympathectomy failed to alter this increase. Intracerebroventricular (i.c.v.) choline (1.5 μmol) administration also increased plasma glucagon; the effect was blocked by central pretreatment with a neuronal type nicotinic acetylcholine receptor antagonist, mecamylamine (50 μg; i.c.v.) or the neuronal choline uptake inhibitor, hemicholinium-3 (20 μg; i.c.v.). These data show that choline, CDP-choline or phosphocholine increases plasma glucagon concentrations by increasing peripheral nicotinic and muscarinic cholinergic neurotransmissions. Central choline also increases plasma glucagon by augmenting central nicotinic cholinergic neurotransmission by acting presynaptically. Stimulation of adrenal medullary catecholamine release and subsequent activation of α2-adrenoceptors are mainly involved in the increase in plasma glucagon induced by choline, CDP-choline or phosphocholine.