title: Intraperitoneal administration of CDP-choline and its cholinergic and pyrimidinergic metabolites induce hyperglycemia in rats: involvement of the sympathoadrenal system.
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 micromol/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 -adrenoceptor antagonist phentolamine or by the 2-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 2-adrenoceptors.
authors.affiliation: Department of Biochemistry, Uludag University School of Medicine, Bursa, Turkey. yesim@uludag.edu.tr
authors.forename: Y O
authors.initials: YO
authors.lastname: Ilcol
authors.forename: M
authors.initials: M
authors.lastname: Cansev
authors.forename: M S
authors.initials: MS
authors.lastname: Yilmaz
authors.forename: E
authors.initials: E
authors.lastname: Hamurtekin
authors.forename: I H
authors.initials: IH
authors.lastname: Ulus
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects* / Q000502:physiology; D000315:Adrenalectomy; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D018674:Adrenergic Antagonists; D001786:Blood Glucose; D018680:Cholinergic Antagonists; D011743:Pyrimidines; D010767:Phosphorylcholine; D003566:Cytidine Diphosphate Choline