PMID- 18561911 OWN - NLM STAT- MEDLINE DCOM- 20081024 LR - 20131121 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 589 IP - 1-3 DP - 2008 Jul 28 TI - Choline, CDP-choline or phosphocholine increases plasma glucagon in rats: involvement of the peripheral autonomic nervous system. PG - 315-22 LID - 10.1016/j.ejphar.2008.05.017 [doi] AB - 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 micromol/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 micromol/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 micromol/kg). While alpha(2)-adrenoceptor blockade or bilateral adrenalectomy attenuated the increase in plasma glucagon evoked by choline compounds, blockade of alpha(1)- or beta-adrenoceptors or chemical sympathectomy failed to alter this increase. Intracerebroventricular (i.c.v.) choline (1.5 micromol) administration also increased plasma glucagon; the effect was blocked by central pretreatment with a neuronal type nicotinic acetylcholine receptor antagonist, mecamylamine (50 microg; i.c.v.) or the neuronal choline uptake inhibitor, hemicholinium-3 (20 microg; 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 alpha(2)-adrenoceptors are mainly involved in the increase in plasma glucagon induced by choline, CDP-choline or phosphocholine. FAU - Cansev, Mehmet AU - Cansev M AD - Department of Pharmacology and Clinical Pharmacology, Uludag University Medical School, Bursa, Turkey. mcansev@uludag.edu.tr FAU - Ilcol, Yesim Ozarda AU - Ilcol YO FAU - Yilmaz, Mustafa Sertac AU - Yilmaz MS FAU - Hamurtekin, Emre AU - Hamurtekin E FAU - Ulus, Ismail H AU - Ulus IH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080524 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Adrenergic alpha-Antagonists) RN - 0 (Adrenergic beta-Antagonists) RN - 0 (Ganglionic Blockers) RN - 0 (Muscarinic Antagonists) RN - 0 (Neurotransmitter Uptake Inhibitors) RN - 0 (Nicotinic Antagonists) RN - 107-73-3 (Phosphorylcholine) RN - 536BQ2JVC7 (Cytidine Diphosphate Choline) RN - 9007-92-5 (Glucagon) RN - N91BDP6H0X (Choline) SB - IM MH - Adrenal Medulla/drug effects/innervation/*metabolism MH - Adrenalectomy MH - Adrenergic alpha-Antagonists/pharmacology MH - Adrenergic beta-Antagonists/pharmacology MH - Animals MH - Autonomic Nervous System/drug effects/*physiology MH - Brain/metabolism MH - Choline/administration & dosage/blood/*metabolism MH - Cytidine Diphosphate Choline/administration & dosage/*metabolism MH - Dose-Response Relationship, Drug MH - Ganglionic Blockers/pharmacology MH - Glucagon/*blood MH - Injections, Intraperitoneal MH - Injections, Intraventricular MH - Male MH - Muscarinic Antagonists/pharmacology MH - Neurotransmitter Uptake Inhibitors/pharmacology MH - Nicotinic Antagonists/pharmacology MH - Phosphorylcholine/administration & dosage/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Sympathectomy, Chemical MH - Time Factors MH - Up-Regulation EDAT- 2008/06/20 09:00 MHDA- 2008/10/25 09:00 CRDT- 2008/06/20 09:00 PHST- 2008/01/20 00:00 [received] PHST- 2008/04/29 00:00 [revised] PHST- 2008/05/19 00:00 [accepted] PHST- 2008/06/20 09:00 [pubmed] PHST- 2008/10/25 09:00 [medline] PHST- 2008/06/20 09:00 [entrez] AID - S0014-2999(08)00561-X [pii] AID - 10.1016/j.ejphar.2008.05.017 [doi] PST - ppublish SO - Eur J Pharmacol. 2008 Jul 28;589(1-3):315-22. doi: 10.1016/j.ejphar.2008.05.017. Epub 2008 May 24.