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.