The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study.
1. This study is concerned with the supply of metabolic substrates for neuronal metabolism. Experiments were carried out to investigate whether mechanisms demonstrated in cultured astrocytes also occurred in vivo; these were cAMP-mediated breakdown of glycogen and glutamate uptake-stimulated release of lactate. 2. In vivo microdialysis was used in freely moving rats. Lactate and glucose in the dialysate were assayed using enzyme-based on-line assays. Drugs were given locally through the dialysis probe. Regional cerebral blood flow was measured using the hydrogen clearance method. 3. There was an increase in dialysate glucose in response to the beta-adrenoceptor agonist isoprenaline and to 8-bromo-cAMP, an analogue of cAMP, the second messenger of beta-adrenoceptor stimulation. The effect of isoprenaline was blocked by the antagonist propranolol. Isoprenaline had no effect on dialysate lactate, which was increased by the glutamate uptake blocker beta-D,L-threohydroxyaspartate (THA). 4. Physiological stimulation of neuronal activity produced an increase in both lactate and glucose. The increase in lactate was depressed in the presence of THA but was unaffected by propranolol. The increase in glucose was blocked by propranolol. Regional cerebral blood flow was increased by physiological stimulation but was unaffected by propranolol. 5. These results demonstrate that physiologically stimulated increases in glucose and lactate in the brain are mediated by different mechanisms.
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK.
A E
AE
Fray
R J
RJ
Forsyth
M G
MG
Boutelle
M
M
Fillenz
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation; D004567:Electrodes, Implanted; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; C011274:3-hydroxyaspartic acid; D001224:Aspartic Acid; D019344:Lactic Acid; D006003:Glycogen; D011433:Propranolol; D005947:Glucose; D007545:Isoproterenol