Effects of ACTH and diabetes on phospholipid metabolism in adrenal mitochondria

Summary Incorporation of 32P into adrenal mitochondrial phospholipids (PL) increased in ACTH-treated rats, but it decreased in diabetics, inspite of the fact that these animals showed adrenal overactivity. Since diabetics did not show increased 11 -hydroxylation, as opposed to ACTH-treated rats, it is suggested that the stimulation of this enzyme activity by exogenous ACTH is related to an increased turnover of PL at the mitochondrial membrane. This process is impaired in diabetics and prevents the stimulation of 11 -hydroxylation.     

NADP-isocitric dehydrogenase of gerbil adrenal mitochondria: support of steroid hydroxylation

In gerbil adrenal cortex the activity of intramitochondrial NADP-linked isocitric dehydrogenase (IDH) is up to 10-fold greater than the NAD-linked IDH. The NADP-IDH, apparent Km 0.58 mM, Vmax 280 nmoles/min/mg mitochondrial protein, appears to be the major source of reducing equivalents to support adrenal mitochondrial steroid 11B- and 19-hydroxylation in this species.     

NADP-isocitric dehydrogenase of gerbil adrenal mitochondria: Support of steroid hydroxylation

Summary In gerbil adrenal cortex the activity of intramitochondrial NADP-linked isocitric dehydrogenase (IDH) is up to 10-fold greater than the NAD-linked IDH. The NADP-IDH, apparent K_m 0.58 mM, V_max 280 nmoles/min/mg mitochondrial protein, appears to be the major source of reducing equivalents to support adrenal mitochondrial steroid 11B- and 19-hydroxylation in this species.     

Effects of epinephrine on plasma fibrinogen levels in rats submitted to tissue injury

Summary Tissue injury (laparotomy) produces an increase in plasma fibrinogen. This increase is inhibited by the removal of the adrenal medulla, but injection of epinephrine in laparotomized-medullectomized rats returns fibrinogen levels to values similar to those observed in only laparotomized rats. Epinephrine administration to laparotomized rats increases the fibrinogen compared with the group of laparotomized rats without treatment, but epinephrine by itself does not modify plasma fibrinogen levels in uninjured rats. Epinephrine is apparently responsible for the increase of plasma fibrinogen in rats subjected to tissue injury, probably through beta adrenergic stimulation.     

Oxygen consumption and biosynthetic function in perfused liver from rats at different stages of development

Changes in mitochondrial function were studied in perfused liver from rats aged 24 – 365 days. Oxygen consumption together with the rates of gluconeogenesis, urea synthesis and ketogenesis were determined. Basal mitochondrial respiration as well as the ability of the liver to synthesize glucose, urea and ketone bodies declined from 24- to 365-day-old rats. On the other hand, on transition from 24 to 60 days the liver oxidation rate of hexanoate, sorbitol and glycerol is enhanced, but not of ketone bodies or palmitate. Our results show that the transition from weaning to middle age is accompanied by defined changes in hepatic substrate oxidation. From the observed time course of the decrease in basal and substrate-stimulated oxygen consumption, it is concluded that in rat liver cells a decline in respiratory chain function, long-chain fatty acid and ketone body metabolism, gluconeogenesis and ureogenesis occurs at a relatively early life stage. Received 19 June 1998; received after revision 11 September 1998; accepted 11 September 1998     

Investigations into the effects of ACTH on the half-life of mitochondrial proteins in the rat adrenal cortex

Summary ACTH elongates the half-life of the mitochondrial proteins from the rat adrenal cortex, and chloramphenicol inhibits this effect of ACTH. The hypothesis is advanced that the ACTH-provoked stabilization of the adrenocortical mitochondrial proteins requires continuous mitochondrial DNA-dependent protein synthesis.     

Investigations into the effects of ACTH on the half-life of mitochondrial proteins in the rat adrenal cortex.

ACTH elongates the half-life of the mitochondrial proteins from the rat adrenal cortex, and chloramphenicol inhibits this effect of ACTH. The hypothesis is advanced that the ACTH-provoked stabilization of the adrenocortical mitochondrial proteins requires continuous mitochondrial DNA-dependent protein synthesis.     

High-voltage electron microscopy of adrenal medulla: Direct connections between mitochondria and catecholamine-storage vesicles

Summary A high-voltage electron microscopic study of adrenal medullary cells from hypoglycemia-stressed rats revealed the existence of tubular channels which create a luminal continuity between the mitochondrial compartment and the catecholamine-storage vesicles. It is suggested that these channels allow for the transfer of materials such as high-energy nucleotides between the mitochondria and the catecholamine-storage vesicles without an intervening membrane.We thank Barbara Coalgate, Lin Cooper, Joann Cox, and the staff at the US Steel HVEM Laboratory for their assistance. This work was supported by NIH-DRR-70-4136, WVU Medical Corporation Research Grants, WVU Senate Research Grant, and West Virginia Heart Association Research Grant.     

Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats

The effect of treatment with acetyl-L-carnitine on hepatic mitochondrial respiration and biosynthetic function in perfused liver from young (90 days) and old (22-24 months) rats was studied. Rats were given a 1.5% (w/v) solution of acetyl-L-carnitine in their drinking water for 1 month and oxygen consumption together with the rate of gluconeogenesis, urea synthesis, and ketogenesis with and without added substrates were measured in perfused liver. Mitochondrial oxygen consumption was also assessed in liver homogenate and isolated mitochondria to determine the maximal capacity for oxidative phosphorylation. Acetyl-L-carnitine treatment almost completely restored the age-dependent decline in oxygen consumption, gluconeogenesis, urea synthesis, and ketogenesis found in perfused liver of old rats to the levels found in young rats. In addition, acetyl-L-carnitine treatment increased oxygen consumption and biosynthetic function in perfused liver from young rats. After acetyl-L-carnitine treatment, we found detectable 3-oxoacyl-CoA-transferase activity associated with a consumption of ketone bodies in young and old rats. Finally, oxygen consumption measured in homogenate and isolated mitochondria did not change with age and acetyl-L-carnitine treatment. Our results show that in perfused liver, acetyl-L-carnitine treatment slows the age-associated decline in mitochondrial respiration and biosynthetic function. In addition, treatment of young rats with acetyl-L-carnitine has a stimulating effect on liver metabolism, probably through an increase in ATP production. Received 25 October 2000; received after revision 14 December 2000; accepted 11 January 2001     

Quantitative immunofluorescence of tyrosine hydroxylase in the adrenal medulla of spontaneously hypertensive rats

Summary The amount of tyrosine hydroxylase protein in the adrenal medulla, which was estimated by a quantitative immunofluorescence method, was higher in spontaneously hypertensive rats than in normotensive control Wistar-Kyoto rats at 4 and 16 weeks of age before and after the development of hypertension.This study was supported by grants from the Ministry of Education, Science and Culture, Japan (No. 59570018). Reprint requests to I.N., Department of Anatomy, School of Medicine, Fujita-Gakuen Health University, Toyoake, Aichi 470-11 (Japan).     

Activity of the reticuloendothelial system following exposure to electric stress and thymectomy

Summary After electric stress stimulation, granulopectic activity is reduced in otherwise normal rats, whereas it appears to be increased in thymectomized animals. The differences between the 2 groups of animals seem to support the hypothesis that the effects of stress upon the overall phagocytic capacity may be mediated by the products of lymphocyte breakdown.The collaboration of Prof. A. Colombi for the statistical analysis of the experimental results is gratefully acknowledged.     

Reserpin und Glykogengehalt der Organe

Summary In fasted white mice, 1–18 h after the injection of 5 mg/kg Reserpine the glycogen content of brain, heart, skeletal muscle and liver is significantly increased (about 100%, in liver nearly 300%). It is suggested that this is due to an enhanced synthesis of glycogen from non-carbohydrate material.Concerning the underlying mechanism, it is pointed out that after reserpine there occurs a release of catecholamines from the adrenal medulla and-by stimulation of the anterior pituitary-an enhanced production of corticoids.Simultaneously with the increase of the brain glycogen, the level of lactic acid is decreased, whereas the ATP-, ADP- and AMP-content of the brain remains practically unaffected.

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Ausgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Corticosterone secretion after neurogenic stress in intact and hypophysectomized rats

Summary The time course of blood and adrenal corticosterone elevation after immobilization stress has been studied in intact and hypophysectomized male rats. The results suggest that the adrenal gland is able to respond to neurogenic stress, increasing the synthesis and release of corticosterone, in the absence of ACTH.     

Inducing effect of clofibrate on alkaline phosphatase and histidine-glyoxylate aminotransferase in rat liver

Summary The activity of plasma membrane alkaline phosphatase and both mitochondrial and peroxisomal histidineglyoxylate aminotransferase was significantly increased in the livers of male rats following treatment with the hypolipidemic drug clofibrate. Cycloheximide or puromycin administration to rats inhibited the effects of clofibrate.     

Stimulation by ACTH of protein synthesis in cultured adrenal cells. Absence of an effect by cyclin AMP]

ACTH stimulates the incorporation of 14C-leucine into proteins of adrenal tumor cells in culture. This stimulation though about 20% over controls is statistically significant. Cyclic AMP did not reproduce the stimulation observed with ACTH.     

Pharmacologic study of several alpha-adrenolytics

Six alpha-adrenoceptor blocking agents have been investigated in dogs and rats. 170 150 and 170 153 have been found the most potent of these agents. At low doses (0,1 microgram/kg) they reversed the pressor response to low doses of adrenaline (0,1 and 0,3 microgram/kg) and suppressed the response to high doses of adrenaline. They reduced the pressor response to noradrenaline. In addition, in dogs 170 150 increased the tachycardia caused by stimulation of the cardiac nerve. The compound prevented and reversed the inhibition caused by clonidine on the effects of cardiac nerve stimulation. 170 153 did not increase the tachycardia caused by cardiac nerve stimulation, but it prevented and reversed the inhibitory effects of clonidine on this stimulation. The results show that 170 150 and 170 153 are potent alpha-adrenoceptor blocking agents acting on both pre and post-synaptic alpha-adrenoceptors which could be interesting pharmacological tools.     

Effect of bilateral adrenalectomy and parenteral betamethasone on gastric mucosal mast cell population in albino rats

Summary The histamine-laden mast cells gastric mucosa in albino rats are shown to degranulate on administration of Betamethasone, but they increase in number in adrenalectomized rats. It is concluded that Betamethasone, and also adrenal glucocorticoids incrase gastric secretion by liberating histamine from mast cells and histamine in turn acts on the gastric glands.     

Effect of bilateral adrenalectomy and parenteral betamethasone on gastric mucosal mast cell population in albino rats.

The histamine-laden mast cells of gastric mucosa in albino rats are shown to degranulate on administration of Betamethasone, but they increase in number in adrenalectomized rats. It is concluded that Betamethasone, and also adrenal glucocorticoids increase gastric secretion by liberating histamine from mast cells and histamine in turn acts on the gastric glands.     

Modulation of hepatic mitochondrial energy efficiency with age

This study was designed to examine the effect of youth-adulthood transition on hepatic mitochondrial energy efficiency. The changes in basal and palmitate-induced proton leak, which contribute to mitochondrial efficiency, were evaluated in mitochondria isolated from the liver of young and adult rats. Alterations in mitochondrial cytochrome oxidase and aconitase specific activities, and in adenine nucleotide translocator content were also assessed. There was no difference in basal proton leak or thermodynamic coupling and efficiency of oxidative phosphorylation in liver mitochondria between the two rat groups. On the other hand, palmitate-induced proton leak increased significantly in adult rats. The function of this uncoupling could be avoidance of elevated formation of reactive oxygen species, which are known to accelerate ageing.Received 17 February 2004; received after revision 30 March 2004; accepted 1 April 2004     

Effect of pylorus ligation on gastric mucosal mast cell population in normal and adrenalectomised albino rats

Summary Pylorus ligation in normal albino rats acts like a stressor leading to degranulation of mast cells in gastric mucosa, thereby decreasing their number. This decrease is less pronounced when pylorus ligation is done in adrenalectomized rats. This implies that action of a stressor on gastric function involves the adrenal steroids which liberate the powerful gastric stimulant histamine from gastric mucosal mast cells.