A role for central postsynaptic alpha 2-adrenoceptors in glucoregulation.
Central or peripheral administration of the alpha 2-adrenoceptor agonist clonidine causes marked hyperglycemia in the rat. It is not clear whether this effect is mediated within the brain at either pre- or postsynaptic alpha 2-adrenoceptors or whether it is due to peripheral alpha 2-agonist actions. We employed computerized mass spectrometry to measure noradrenaline (NA) and its primary neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG) in the medial basal hypothalamus of rats treated acutely with clonidine, the alpha 2-antagonist yohimbine, the postganglionic noradrenergic blocker guanethidine and the neuroglycopenic agent 2-deoxy-D-glucose (2-DG). That clonidine's hyperglycemic effect was due, in part, to an action at central alpha 2-adrenoceptors was indicated by the ability of guanethidine to significantly inhibit the glucose response. Because of clonidine's inhibition of hypothalamic NA release (assessed by the DHPG/NA ratio), presumably by presynaptic agonism, these data indicated that postsynaptic receptor stimulation by clonidine was involved in activating glucose release. Yohimbine markedly increased the hypothalamic DHPG/NA ratio, reflecting presynaptic stimulation of NA release, but at the same time inhibited the hyperglycemic response due to 2-DG administration. This latter effect to block hyperglycemia is consistent with antagonism of postsynaptic alpha 2-adrenoceptors involved in mediating hepatic glucose output. These data indicate a major role for postsynaptic alpha 2-adrenoceptors in glucoregulation.
Smythe
G A
GA
Department of Chemical Pathology, St. Vincent's Hospital, Sydney, N.S.W., Australia.
Edwards
S R
SR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D006145:Guanethidine / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013569:Synapses; D015016:Yohimbine / Q000494:pharmacology
D001786:Blood Glucose; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D008734:Methoxyhydroxyphenylglycol; D003000:Clonidine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D006145:Guanethidine