GabaB receptors activation in the NTS blocks the glycemic responses induced by carotid body receptor stimulation.

The carotid body receptors participate in glucose regulation sensing glucose levels in blood entering the cephalic circulation. The carotid body receptors information, is initially processed within the nucleus tractus solitarius (NTS) and elicits changes in circulating glucose and brain glucose uptake. Previous work has shown that gamma-aminobutyric acid (GABA) in NTS modulates respiratory reflexes, but the role of GABA within NTS in glucose regulation remains unknown. Here we show that GABA(B) receptor agonist (baclofen) or antagonists (phaclofen and CGP55845A) locally injected into NTS modified arterial glucose levels and brain glucose retention. Control injections outside NTS did not elicit these responses. In contrast, GABA(A) agonist and antagonist (muscimol or bicuculline) produced no significant changes in blood glucose levels. When these GABAergic drugs were applied before carotid body receptors stimulation, again, only GABA(B) agonist or antagonist significantly affected glycemic responses; baclofen microinjection significantly reduced the hyperglycemic response and brain glucose retention observed after carotid body receptors stimulation, while phaclofen produced the opposite effect, increasing significantly hyperglycemia and brain glucose retention. These results indicate that activation of GABA(B), but not GABA(A), receptors in the NTS modulates the glycemic responses after anoxic stimulation of the carotid body receptors, and suggest the presence of a tonic inhibitory mechanism in the NTS to avoid hyperglycemia.

Carotid chemoreceptor reflex modulation by arginine-vasopressin microinjected into the nucleus tractus solitarius in rats.

BACKGROUND: In addition to their role of sensing O2, pH, CO2, osmolarity and temperature, carotid body receptors (CBR) were proposed by us and others to have a glucose-sensing role in the blood entering the brain, integrating information about blood glucose and O2 levels essential for central nervous system (CNS) metabolism. The nucleus tractus solitarius (NTS) is an important relay station in central metabolic control and receives signals from peripheral glucose-sensitive hepatoportal afferences, from central glucose-responsive neurons in the brainstem and from CBR and arginine-vasopressin (AVP)-containing axons from hypothalamic nuclei. METHODS: In normal Wistar rats anesthetized with pentobarbital, permanent cannulas were placed stereotaxically in the NTS. Glucose changes were induced in vivo after CBR stimulation with sodium cyanide (NaCN-5 microg/100 g), preceded by an infusion of AVP [(10 or 40 pmol/100 nL of artificial cerebrospinal fluid) aCSF] or an antagonist for V1a receptors (anti-glycogenolytic vasopressin analogue-VP1-A) (100 pmol/100 nL of aCSF) into the NTS. RESULTS: CBR stimulation after an AVP infusion (larger dose) into the NTS resulted in a significantly higher arterial glucose and lower brain arterial-venous glucose difference. In the same way, VP1-A administration in the NTS significantly decreased the effects observed after AVP priming before CBR stimulation or preceding the CBR stimulation, alone. CONCLUSIONS: We propose that AVP in the NTS could participate in glucose homeostasis, modulating the information arising in CBR after histotoxic-anoxia stimulation.

Arginine-vasopressin mediates central and peripheral glucose regulation in response to carotid body receptor stimulation with Na-cyanide.

Hypoxic stimulation of the carotid body receptors (CBR) results in a rapid hyperglycemia with an increase in brain glucose retention. Previous work indicates that neurohypophysectomy inhibits this hyperglycemic response. Here, we show that systemic arginine vasopressin (AVP) induced a transient, but significant, increase in blood glucose levels and increased brain glucose retention, a response similar to that observed after CBR stimulation. Comparable results were obtained after intracerebral infusion of AVP. Systemic AVP-induced changes were maintained in hypophysectomized rats but were not observed after adrenalectomy. Glycemic changes after CBR stimulation were inhibited by pharmacological blockage of AVP V1a receptors with a V1a-selective receptor antagonist ([beta-Mercapto-beta,beta-cyclopentamethylenepropionyl1,O-me-Tyr2, Arg8]-vasopressin). Importantly, local application of micro-doses of this antagonist to the liver was sufficient to abolish the hyperglycemic response after CBR stimulation. These results suggest that AVP is a mediator of the hyperglycemic reflex and cerebral glucose retention following CBR stimulation. We propose that hepatic activation of AVP V1a receptors is essential for this hyperglycemic response.

Induction of brain glucose uptake by a factor secreted into cerebrospinal fluid.

It is well established that the carotid body receptors (CBR), at the bifurcation of the carotid artery, inform the brain of changes in the concentration of CO(2) and O(2) in arterial blood. More recent work suggests that these receptors are also extremely sensitive to blood glucose levels suggesting that they may play an important role as sensors of blood components important for brain energy metabolism. Much less is known about changes in brain glucose metabolism in response to CBR activation. Here we show that 2-8 min after local injection of sodium cyanide (NaCN) into the CBR or after electrical stimulation of the carotid sinus nerve in dogs and rats, brain glucose uptake increased fourfold. Cerebrospinal fluids (CSF) transferred from dogs, 2-8 min after CBR stimulation, into the cisterna magna of non-stimulated dogs or rats induced a similar increase in brain glucose uptake. CSF from stimulated dogs was also active when injected intravenously in anesthetized or awake rats. The activity was destroyed when the stimulated CSF was heated to 100 degrees C or treated with trypsin. We conclude that a peptide important for brain glucose regulation appears in the CSF shortly after CBR stimulation.

Influence of the pituitary gland on the immune response in young rats

The response of hypophysectomized (HYPOX) and sham-operated (S-HYPOX) female and male Wistar young rats (8 weeks old) to antigenic stimulation was compared. Humoral antigenic responses against hemocyanin were measured by ELISA. [3H]thyimidine incorporation into cultured splen cells was used to determine proliferative response to concanavalin A (ConA) or antigenic stimulation. Anti-hemocyanin serum titers in the HYPOX animals was about half of that observed in control S-HYPOX rats. Similarly, the cellular proliferative response was significantly decreased in HYPOX animals when compared to S-HYPOX rats; the blastogenic response to hemocyanin in UC rats (which did not receive the antigen injection) was close to zero. S-HYPOX control rats responded to direct ConA stimulation as UC controls. Body weight and the weight of pituitary target organs (adrenal, thyroid, ovary and testes) was about 1/4 of that of controls. Hypophysectomy also resulted in a striking reduction in spleen weight. These results indicate that the pituitary gland is involved in cellular and humoral immune regulation in young rats. (AU)

Influence of the pituitary gland on the immune response in young rats

The response of hypophysectomized (HYPOX) and sham-operated (S-HYPOX) female and male Wistar young rats (8 weeks old) to antigenic stimulation was compared. Humoral antigenic responses against hemocyanin were measured by ELISA. [3H]thyimidine incorporation into cultured splen cells was used to determine proliferative response to concanavalin A (ConA) or antigenic stimulation. Anti-hemocyanin serum titers in the HYPOX animals was about half of that observed in control S-HYPOX rats. Similarly, the cellular proliferative response was significantly decreased in HYPOX animals when compared to S-HYPOX rats; the blastogenic response to hemocyanin in UC rats (which did not receive the antigen injection) was close to zero. S-HYPOX control rats responded to direct ConA stimulation as UC controls. Body weight and the weight of pituitary target organs (adrenal, thyroid, ovary and testes) was about 1/4 of that of controls. Hypophysectomy also resulted in a striking reduction in spleen weight. These results indicate that the pituitary gland is involved in cellular and humoral immune regulation in young rats.

Developmental changes in blood glucose and tissue carbohydrates in the fetal rat: effects of insulin and adrenaline

The ontogeny of glucose regulation was studied in the rat by measuring the levels of plasma glucose, tissue glucose and tissue glycogen from fetal day 15 (E15) to adulthood. Since insulin and adrenaline are important glucose regulators in the adult, we also tested the effects of these hormones on above variables. The main findings are the following: 1) Umbilical blood glucose was very low (25 mg/100 ml) from E15 to E19, increasing to 66 mg/ml by E21 but still below maternal levels (110 mg/100 ml). 2) Umbilical venous-arterial (VEN-ART) glucose differences were very small (1 mg/100 ml) from E15 to E17, increased to 6 mg/100 ml by E19, but dropped again becoming negative (-l5 mg/100 ml) just before birth when umbilical arterial blood glucose rose above venous blood glucose. 3) Glucose and glycogen concentrations rose drastically in liver towards the end of gestation. 4) Tissue glycogen and, to a much lesser degree, glucose, fell after birth to rise again in adulthood. 5) Insulin injection caused an increase in liver glycogen from E17 onwards, and also increased glycogen in brain and placenta on E19. However, insulin decreased glycogen in brain and kidney by E21. 6) Adrenaline caused an increase in the umbilical venous-arterial glucose difference at E15 and E17 with a concomitant increase in liver, brain and heart glycogen at E15. By E21 the response of liver glycogen to adrenaline was drastically reversed. Our data suggest that the mechanism regulating glucose homeostasis changes half way through fetal development. Tissue self-regulation is replaced with a centralized mechanism similar to that of the adult. This occurs just before birth as the liver becomes a reservoir for carbohydrates and responsive to insulin and adrenaline (AU)

Developmental changes in blood glucose and tissue carbohydrates in the fetal rat: effects of insulin and adrenaline

The ontogeny of glucose regulation was studied in the rat by measuring the levels of plasma glucose, tissue glucose and tissue glycogen from fetal day 15 (E15) to adulthood. Since insulin and adrenaline are important glucose regulators in the adult, we also tested the effects of these hormones on above variables. The main findings are the following: 1) Umbilical blood glucose was very low (25 mg/100 ml) from E15 to E19, increasing to 66 mg/ml by E21 but still below maternal levels (110 mg/100 ml). 2) Umbilical venous-arterial (VEN-ART) glucose differences were very small (1 mg/100 ml) from E15 to E17, increased to 6 mg/100 ml by E19, but dropped again becoming negative (-l5 mg/100 ml) just before birth when umbilical arterial blood glucose rose above venous blood glucose. 3) Glucose and glycogen concentrations rose drastically in liver towards the end of gestation. 4) Tissue glycogen and, to a much lesser degree, glucose, fell after birth to rise again in adulthood. 5) Insulin injection caused an increase in liver glycogen from E17 onwards, and also increased glycogen in brain and placenta on E19. However, insulin decreased glycogen in brain and kidney by E21. 6) Adrenaline caused an increase in the umbilical venous-arterial glucose difference at E15 and E17 with a concomitant increase in liver, brain and heart glycogen at E15. By E21 the response of liver glycogen to adrenaline was drastically reversed. Our data suggest that the mechanism regulating glucose homeostasis changes half way through fetal development. Tissue self-regulation is replaced with a centralized mechanism similar to that of the adult. This occurs just before birth as the liver becomes a reservoir for carbohydrates and responsive to insulin and adrenaline

Consumo de glucosa bajo acción de una cocarboxilasa no degradable, utilizando cianuro como estimulante / Consuption of glucose under the action of a non degradable cocaiboxilase using cyamide as stimulant

Se determinó la variación del consumo de glucosa, por acción de una cocarboxilasa no degradable en animal sano y en animal intoxicado con cianuro como estimulante, midiendo las alteraciones electrofisiológicas de los quimiorreceptores aórticos y carotídeos. La conclusión fue que la cocarboxilasa no degradable inteviene en el metabolismo de la glucosa favorecendo funcional y notoriamente al músculo cardiaco sometido a la anoxia del cianuro, el cual reproduce masivametne los efectos de la isquemia