Intraperitoneal administration of CDP-choline and its cholinergic and pyrimidinergic metabolites induce hyperglycemia in rats: involvement of the sympathoadrenal system

• Published in: Archives of physiology and biochemistry Vol. 113; no. 4-5; pp. 186 - 201
• Main Authors: Ilcol, Y. O., Cansev, M., Yilmaz, M. S., Hamurtekin, E., Ulus, I. H.
• Format: Journal Article
• Language: English
• Published: Basingstoke Informa UK Ltd 01.10.2007; Taylor & Francis
• Subjects: Adrenal Medulla - drug effects; Adrenal Medulla - physiology; Adrenalectomy; Adrenergic Antagonists - pharmacology; Animals; Biological and medical sciences; Blood Glucose - metabolism; CDP-choline; choline; Cholinergic Antagonists - pharmacology; CMP; cytidine; Cytidine Diphosphate Choline - administration & dosage; Cytidine Diphosphate Choline - blood; Cytidine Diphosphate Choline - pharmacology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; glucose; Humans; hyperglycemia; Hyperglycemia - chemically induced; Hyperglycemia - metabolism; Injections, Intraperitoneal; metabolism; Phosphorylcholine - administration & dosage; Phosphorylcholine - blood; Phosphorylcholine - pharmacology; Pyrimidines - administration & dosage; Pyrimidines - blood; Pyrimidines - pharmacology; Rats; Rats, Wistar; Sympathectomy, Chemical; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Time Factors; UMP; uridine; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Sympathoadrenal system; Rat; CDP-choline; Metabolite; Rodentia; CMP; cytidine; Glucose; Metabolism; Vertebrata; Hyperglycemia; Mammalia; Choline; Uridine; UMP; Pyrimidine nucleoside
• ISSN: 1381-3455; 1744-4160
• DOI: 10.1080/13813450701531243

Abstract CDP-choline is an endogenous metabolite in phosphatidylcholine biosynthesis. Exogenous administration of CDP-choline has been shown to affect brain metabolism and to exhibit neuroprotective actions. On the other hand, little is known regarding its peripheral actions. Intraperitoneal administration of CDP-choline (200 - 600 μmol kg) induced a dose- and time-dependent hyperglycemia in rats. Hyperglycemic response to CDP-choline was associated with several-fold elevations in serum concentrations of CDP-choline and its metabolites. Intraperitoneal administration of phosphocholine, choline, cytidine, cytidine monophosphate, cytidine diphosphate, cytidine triphosphate, uridine, uridine monophosphate, uridine diphosphate and uridine triphosphate also produced significant hyperglycemia. Pretreatment with atropine methyl nitrate failed to alter the hyperglycemic responses to CDP-choline and its metabolites whereas hexamethonium, the ganglionic nicotinic receptor antagonist which blocks nicotinic cholinergic neurotransmission at the autonomic ganglionic level, blocked completely the hyperglycemia induced by CDP-choline, phosphocholine and choline, and attenuated the hyperglycemic response to cytidine monophosphate and cytidine. Increased blood glucose following CDP-choline, phosphocholine and choline was accompanied by elevated plasma catecholamine concentrations. Hyperglycemia elicited by CDP-choline and its metabolites was entirely blocked either by pretreatment with a nonselective α-adrenoceptor antagonist phentolamine or by the α2-adrenoceptor antagonist, yohimbine. Hyperglycemic responses to CDP-choline, choline, cytidine monophosphate and cytidine were not affected by chemical sympathectomy, but were prevented by bilateral adrenalectomy. Phosphocholine-induced hyperglycemia was attenuated by bilateral adrenalectomy or by chemical sympathectomy. These data show that CDP-choline and its metabolites induce hyperglycemia which is mediated by activation of ganglionic nicotinic receptors and stimulation of catecholamine release that subsequently activates α2-adrenoceptors.