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 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.
Department of Pharmacology and Clinical Pharmacology, Uludag University Medical School, Bursa, Turkey. mcansev@uludag.edu.tr <mcansev@uludag.edu.tr>
Mehmet
M
Cansev
Yesim Ozarda
YO
Ilcol
Mustafa Sertac
MS
Yilmaz
Emre
E
Hamurtekin
Ismail H
IH
Ulus
D000313:Adrenal Medulla / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D000315:Adrenalectomy; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005730:Ganglionic Blockers / Q000494:pharmacology; D005934:Glucagon / Q000097:blood*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013563:Sympathectomy, Chemical; D013997:Time Factors; D015854:Up-Regulation
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D005730:Ganglionic Blockers; D018727:Muscarinic Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D018733:Nicotinic Antagonists; D010767:Phosphorylcholine; D003566:Cytidine Diphosphate Choline; D005934:Glucagon; D002794:Choline