A rapid head-space method for ethyl alcohol determination in saliva samples

At neutral pH, tetraphenylboron dissolved in 3-heptanone extracts acetylcholine but not acetylcarnitine from aqucous media. At acid pH, both acetylcholine and acetylcarnitine are extracted. A pH curve of the efficiency of extraction of acetylcholine and acetylearnitine is given and the method of chemical synthesis of [1-acetyl-¹⁴C]carnitine is deseribed.     

Carnitine: transport and physiological functions in the brain

Carnitine (4-N-trimethylammonium-3-hydroxybutyric acid), a compound necessary for a transfer of fatty acids for their oxidation within the cell, accumulates in brain although β-oxidation of fatty acids is very low in neurons. Carnitine accumulates to lower extent in the brain than in peripheral tissues and the mechanism of its transport through the blood–brain barrier is discussed, with the involvement of two transporters, OCTN2 and B^0,+ being presented. A limitation by the blood–brain barrier of carnitine supply for the brain and the mechanism of its transport to neural cells by a protein belonging to neurotransmitters' transporters superfamily is further discussed.

Due to the beneficial effects of administration of acetylcarnitine in case of patients with dementia, the role of this acylcarnitine is presented in the context of neuronal cell metabolism and the role of acetylcarnitine in the synthesis of acetylcholine. The roles of long-chain acyl derivatives of carnitine, in particular palmitoylcarnitine, responsible for interaction with the membranes, lipids acylation and specific interactions with proteins have been summarized. Stimulation of protein palmitoylation and a possibility of changing the acylation status of G proteins is described, as well as interaction of palmitoylcarnitine with protein kinase C. Diminished interaction of the isoform δ of this kinase with GAP-43 (B-50, neuromodulin), whose expression increases upon accumulation of either carnitine or palmitoylcarnitine points to a possible regulation of differentiation by these compounds and their role in neuroregeneration.     

Upregulation of mammary gland OCTNs maintains carnitine homeostasis in suckling infants

Background: Transport of l-carnitine, essential cofactor of fatty acid metabolism, into breast milk is critical for the normal growth and development of the suckling infant. Objective: To increase understanding of developmental expression of carnitine/organic cation (Octn) transporter family at different stages of murine breast development for carnitine delivery. Methods: We applied our transporter-specific antibodies to mOctn1, mOctn2 and mOctn3 to sections of mammary glands of virginal non-lactating, pregnant, late lactating and post-lactating C3H females. Results: We demonstrated differential expression of mOctn1, -2 and -3 in epithelial ducts, specialized myoepithelial cells and fatty stroma. There was notable upregulation of all three Octns and mRNA by RT-PCR concurrent with an increase in epithelial ducts in breasts of pregnant (15 days gestation) and lactating mice (15-days post-partum) compared to virginal 6 week old females, and notable downregulation in expression of Octns 15 days after cessation of lactation. In lactating murine mammary gland at 15 days post-partum, there was a marked increase of fat globules in epithelial ducts. Octn1 and Octn2 had similar expression patterns in lactating gland cells which formed fat globules that were exocytosed into the lumen of alveoli along with transporters Octn1 and Octn2. Octn3 was primarily localized to myoepithelial cells surrounding the ducts at all stages of breast development. Conclusions: There is a dynamic upregulation of the Octn family in pregnant and lactating breasts which likely provides the suckling infant with adequate carnitine for the rapid postnatal upregulation of fatty acid oxidation and ketogenesis critical for cerebral energy metabolism during fasting hypoglycemia.     

Carnitine and derivatives in rat tissues

1. Free carnitine, acetylcarnitine, short-chain acylcarnitine and acid-insoluble carnitine (probably long-chain acylcarnitine) have been measured in rat tissues. 2. Starvation caused an increase in the proportion of carnitine that was acetylated in liver and kidney; at least in liver fat-feeding had the same effect, whereas a carbohydrate diet caused a very low acetylcarnitine content. 3. In heart, on the other hand, starvation did not cause an increase in the acetylcarnitine/carnitine ratio, whereas fat-feeding caused a decrease. The acetylcarnitine content of heart was diminished by alloxan-diabetes or a fatty diet, but not by re-feeding with carbohydrate. 4. Under conditions of increased fatty acid supply the acid-insoluble carnitine content was increased in heart, liver and kidney. 5. The acylation state of carnitine was capable of very rapid change. Concentrations of carnitine derivatives varied with different methods of obtaining tissue samples, and very little acid-insoluble carnitine was found in tissues of rats anaesthetized with Nembutal. In liver the acetylcarnitine (and acetyl-CoA) content decreased if freezing of tissue samples was delayed; in heart this caused an increase in acetylcarnitine. 6. Incubation of diaphragms with acetate or dl-β-hydroxybutyrate caused the acetylcarnitine content to become elevated. 7. Perfusion of hearts with fatty acids containing an even number of carbon atoms, dl-β-hydroxybutyrate or pyruvate resulted in increased contents of acetylcarnitine and acetyl-CoA. Accumulation of these acetyl compounds was prevented by the additional presence of propionate or pentanoate in the perfusion medium; this prevention was not due to extensive propionylation of CoA or carnitine. 8. Perfusion of hearts with palmitate caused a severalfold increase in the content of acid-insoluble carnitine; this increase did not occur when propionate was also present. 9. Comparison of the acetylation states of carnitine and CoA in perfused hearts suggests that the carnitine acetyltransferase reactants may remain near equilibrium despite wide variations in their steady-state concentrations. This is not the case with the citrate synthase reaction. It is suggested that the carnitine acetyltransferase system buffers the tissue content of acetyl-CoA against rapid changes.     

Aluminum-Induced Cholinergic Deficits in Different Brain Parts and Its Implications on Sociability and Cognitive Functions in Mouse

Aluminum is associated with etiology of many neurodegenerative diseases specially Alzheimer’s disease. Chronic exposure to aluminum via drinking water results in aluminum deposition in the brain that leads to cognitive deficits. The study aimed to determine the effects of aluminum on cholinergic biomarkers, i.e., acetylcholine level, free choline level, and choline acetyltransferase gene expression, and how cholinergic deficit affects novel object recognition and sociability in mice. Mice were treated with AlCl₃ (250 mg/kg). Acetylcholine level, free choline level, and choline acetyltransferase gene expression were determined in cortex, hippocampus, and amygdala. The mice were subjected to behavior tests (novel object recognition and social novelty preference) to assess memory deficits. The acetylcholine level in cortex and hippocampus was significantly reduced in aluminum-treated animals, as compared to cortex and hippocampus of control animals. Acetylcholine level in amygdala of aluminum-treated animals remained unchanged. Free choline level in all the three brain parts was found unaltered in aluminum-treated mice. The novel object recognition memory was severely impaired in aluminum-treated mice, as compared to the control group. Similarly, animals treated with aluminum showed reduced sociability compared to the control mice group. Our study demonstrates that aluminum exposure via drinking water causes reduced acetylcholine synthesis in spite of normal free choline availability. This deficit is caused by reduced recycling of acetylcholine due to lower choline acetyltransferase level. This cholinergic hypofunction leads to cognitive and memory deficits. Moreover, hippocampus is the most affected brain part after aluminum intoxication.     

Age-related loss of DNA repair synthesis in isolated rat myocardial cells

Singly isolated beating heart cells from newborn rats performed unscheduled DNA synthesis (‘repair’ synthesis) when irradiated with ultraviolet light in vitro. Repair synthesis could not be induced in beating cardiac cells isolated from adult animals (3–12 months old).     

Carnitine acetyltransferase in pea cotyledon mitochondria

Purified pea cotyledon mitochondria did not oxidise acetyl-CoA in the presence of carnitine. However, acetylcarnitine was oxidised. It was concluded that acetylcarnitine passed through the mitochondrial membrane barrier but acetyl-CoA did not. Only a sensitive radioactive assay detected carnitine acetyltransferase in intact mitochondrion or intact mitoplast preparations. When the mitochondria or mitoplasts were burst, acetyl-CoA substrate was available to the matrix carnitine acetyltransferase and a high activity of the enzyme was measured. The inner mitochondrial membrane is there-fore the membrane barrier to acetyl-CoA but acetylcarnitine is suggested to be transported through this membrane via an integral carnitine: acylcarnitine translocator. Evidence is presented to indicate that when the cotyledons from 48-h-grown peas are oxidising pyruvate, acetylcarnitine formed in the mitochondrial matrix by the action of matrix carnitine acetyltransferase may be transported to extra-mitochondrial sites via the membrane translocator.     

Aspects of carnitine ester metabolism in sheep liver

1. Carnitine acetyltransferase (EC 2.3.1.7) activity in sheep liver mitochondria was 76nmol/min per mg of protein, in contrast with 1.7 for rat liver mitochondria. The activity in bovine liver mitochondria was comparable with that of sheep liver mitochondria. Carnitine palmitoyltransferase activity was the same in both sheep and rat liver mitochondria. 2. The [free carnitine]/[acetylcarnitine] ratio in sheep liver ranged from 6:1 for animals fed ad libitum on lucerne to approx. 1:1 for animals grazed on open pastures. This change in ratio appeared to reflect the ratio of propionic acid to acetic acid produced in the rumen of the sheep under the two dietary conditions. 3. In sheep starved for 7 days the [free carnitine]/[acetylcarnitine] ratio in the liver was 0.46:1. The increase in acetylcarnitine on starvation was not at the expense of free carnitine, as the amounts of free carnitine and total acid-soluble carnitine rose approximately fivefold on starvation. An even more dramatic increase in total acid-soluble carnitine of the liver was seen in an alloxan-diabetic sheep. 4. The [free CoA]/[acetyl-CoA] ratio in the liver ranged from 1:1 in the sheep fed on lucerne to 0.34:1 for animals starved for 7 days. 5. The importance of carnitine acetyltransferase in sheep liver and its role in relieving ;acetyl pressure' on the CoA system is discussed.     

Metabolism of intracerebrally injected mevalonate in brain of suckling and young adult rats

We have investigated the in vivo metabolism via sterol and nonsterol pathways of intracerebrally injected mevalonate (MVA) in brains from suckling (10-day-old) and young adult (60-day-old) rats. Results of our study indicated that increasing the amounts of MVA injected increased MVA incorporation into all the lipid fractions examined. The incorporation of MVA into nonsaponiable lipids (NSF) and digitonin precipitable sterols (DPS) was similar in brains from adult and suckling rats. In brain tissue from both suckling and young adult rats the synthesis of dolichol from MVA varied with the amounts of MVA injected. Significant amounts of MVA were recovered in phosphorylated and free polyprenols (farnesol and geraniol) in brain tissue from rats of both ages. Also in both groups of animals, the amounts of MVA incorporated in phosphorylated and free farnesol were higher than the amounts recovered in either, phosphorylated or free geraniol. The amounts of MVA incorporated into the prenoic/fatty acid fraction by brain tissue from both suckling and young adult rats were less than 1% of the total MVA incorporated (nonsaponifiable and saponifiable lipids). Incorporation of MVA into the prenoic/fatty acid fraction by brain tissue was higher in suckling than in young adult rats. These data indicate that the brain tissue from suckling and young adult rats do not differ in their capacity to metabolize MVA into squalene and sterols and that in brain, metabolism of MVA by a shunt pathway is minimal. This suggests that in vivo regulation of cholesterol synthesis during brain development must occur at a step(s) in the sterol synthetic pathway prior to mevalonate, and that metabolism of mevalonate by shunt pathway did not play a role in the developmental regulation of brain sterol synthesis. The data also suggest that in both groups of animals the synthesis of squalene by synthetase may in part control brain sterol synthesis and the synthesis of dolichol is regulated by MVA concentration in the tissue.     

Enzymic hydrolysis of acetylcarnitine in liver from rats, sheep and cows

1. The enzymic utilization of O-acetyl-l-carnitine other than via carnitine acetyltransferase (EC 2.3.1.7) was investigated in liver homogenates from rats, sheep and dry cows. 2. An enzymic utilization of O-acetyl-l-carnitine via hydrolysis of the ester bond to yield stoicheiometric quantities of acetate and l-carnitine was demonstrated; 0.55, 0.53 and 0.30mumol of acetyl-l-carnitine were utilized/min per g fresh wt. of liver homogenates from rats, sheep and dry cows respectively. 3. The acetylcarnitine hydrolysis activity was not due to a non-specific esterase or non-specific cholinesterase. O-Acetyl-d-carnitine was not utilized. 4. The activity was associated with the enriched outer mitochondrial membrane fraction from rat liver. Isolation of this fraction resulted in an eightfold purification of acetylcarnitine hydrolase activity. 4. The K(m) for this acetylcarnitine utilization was 2mm and 1.5mm for rat and sheep liver homogenates respectively. 6. There was a significant increase in acetylcarnitine hydrolase in rats on starvation and cows on lactation and a significant decrease in sheep that were severely alloxan-diabetic. 7. The physiological role of an acetylcarnitine hydrolase is discussed in relation to coupling with carnitine acetyltransferase for the relief of ;acetyl pressure'.     

Variable effect of ghrelin administration on pancreatic development in young rats. Role of insulin-like growth factor-1.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been primarily isolated from the human and rat stomach. Ghrelin has been shown to stimulate appetite and fat deposition in adult rats and humans. The aim of this study was to investigate the effect of ghrelin administration on pancreatic growth in suckling, weaned and peripubertal seven week old rats. Rats were treated with saline or ghrelin (4, 8 or 16 nmol/kg/dose) intraperitoneally twice a day: suckling rats were treated for 7 or 14 days starting from the first postnatal day, three week old weaned rats and seven weeks old rats were treated for 5 days. Treatment with ghrelin did not affect animal weight in suckling or weaned rats, whereas in young seven week old rats, ghrelin caused a significant increase in body weight. Ghrelin decreased food intake in weaned rats; whereas in seven week old rats, food intake was enhanced. In suckling rats, ghrelin decreased the pancreatic weight, pancreatic amylase content, DNA synthesis and DNA content. In contrast, ghrelin increased pancreatic weight, DNA synthesis, DNA content and amylase content in weaned or young seven week old rats. Pancreatic blood flow was not affected by ghrelin in any group of rats tested. Ghrelin increased serum level of growth hormone in all rats. This effect was weak in suckling rats, higher in weaned and the highest in seven week old animals. Ghrelin did not affect serum level of insulin-like growth factor-1 (IGF-1) in suckling rats. In weaned and in seven week old rats, treatment with ghrelin caused increase in serum level of IGF-1. We conclude that ghrelin reduces pancreatic growth in suckling rats; whereas in weaned and young seven week old animals, treatment with ghrelin increases pancreatic growth. This biphasic effect of ghrelin in young animals on pancreatic growth seems to be related to age-dependent changes of the release of anabolic IGF-1.     

Fatty acid oxidation in isolated rat liver mitochondria. Developmental changes and their relation to hepatic levels of carnitine and glycogen and to carnitine acyltransferase activity

Prompted by an apparent relationship between ketosis and fatty acid utilization, we studied the capacities for fatty acid oxidation through β-oxidation and Krebs cycle in liver mitochondria isolated from fetal and suckling rats. Rates of state 3 oxidation, as measured by oxygen consumption, were low for both palmitylcarnitine and palmityl CoA plus carnitine at 2 days before term and at birth, but increased at least ninefold during the first 8 days of life and at least sixfold during the remaining suckling period. Despite these sharp increases, oxygen consumption in suckling rats did not exceed the value for fed adult rats. Also, the rates of state 3 oxidation of succinate were low in suckling rats. Respiratory control indices, determined with each of the three substrates, were lower in suckling rats than fed adults. By contrast, ratios of fatty acyl ester to succinate oxidation, a relative measure of the oxidation of palmitylcarnitine and palmityl CoA, were 21–66% and 27–77% higher in suckling than in fed adult rats. The increased ratios indicate that the capacity for fatty acid oxidation is higher during postnatal development than in the fetal stage or adulthood. The oxidation capacity was inversely related to glycogen content in the liver. Although hepatic carnitine concentration and carnitine palmityltransferase activity increased during suckling period, they are not rate limiting for fatty acid oxidation. Studies of the partitioning of fatty acids showed that about two-thirds of the fatty acid oxidized through β-oxidation did not enter Krebs cycle for further oxidation. These results support our working hypothesis that ketosis of suckling rats stems from rapid oxidation of fatty acids and increased partitioning of acetyl CoA into ketogenesis.     

Ester composition of carnitine in the perfusate of liver and in the plasma of donor rats

When the carnitine pool of fed rats was labelled with tritium, in non-recirculating perfusate of their liver 44% of acid-soluble 3H activity was identified as free carnitine and 47% as short-chain acylcarnitine. Of the latter component acetylcarnitine accounted for 30% and propionylcarnitine for 10% of total acid-soluble. In plasma the contribution of short-chain acylcarnitines to total carnitine in fed, fasted and diabetic rats was 15.6%, 43.1% and 48.0%, respectively. Recirculating perfusion of livers from the same animals revealed that livers from fed rats released short-chain acylcarnitines as much as 56.2% of total and this proportion did not increase further in the other two groups. At the same time, ketone bodies in the perfusate increased gradually in the fed, fasted and diabetic group, paralleling the plasma ketone levels. Although liver supplies the organism with carnitine the increment of plasma short-chain acylcarnitines seen in ketosis is not a result of some extra output by the liver.     

Ontogeny of T-cell mitogen response in Lewis rats. III. Juvenile adherent suppressor cells block adult mitogen responses

Spleen cells from suckling female Lewis rats (4 to 20 days old) were able to suppress mitogenic responses to concanavalin A (Con A) and phytohemagglutinin (PHA) of spleen or thymus cells from adult female Lewis rats and thymus cells from suckling Lewis rats. Thymus cells from suckling rats were unable to suppress adult spleen cell mitogenic responses to Con A. Removal of carbonyl iron (cFe)-, plastic-, or nylon-wool-adherent cells removed the suppressive action of juvenile spleen cells, but irradiation did not. Separated plastic-adherent spleen cells from suckling animals suppressed adult mitogenic responses to Con A. at optimal Con A doses 2-mercaptoethanol (2-ME, 2 X 10(-5) M) abolished the suppressive effect of juvenile cells, however, at the hyperoptimal dose of Con A (125 micrograms/ml) even higher doses of 2-ME did not relieve suppression by juvenile cells. These suppressor cells in suckling pups were affected by early weaning which decreased suppression, resulting in enhanced mitogenic responses of juvenile cells and removal of the ability to suppress adult mitogenic response.     

The effect of acute and prolonged ethanol treatment on the concentrations of coenzyme A, carnitine and their derivatives in rat liver

1. CoA, acetyl-CoA, long-chain acyl-CoA, carnitine, acetylcarnitine and long-chain acylcarnitine were measured in rat liver under various conditions. 2. Starvation caused an increase in the contents of these intermediates, except that of carnitine. 3. A single dose of ethanol had no effect on CoA content, whereas those of acetyl-CoA, acetylcarnitine and carnitine were increased and those of long-chain acyl-CoA and acylcarnitine were decreased. 4. Four weeks' adaptation to ethanol consumption did not change the effect of ethanol administration on these metabolites. 5. It is suggested that ethanol directly increases hepatic fatty acid synthesis and esterification. It is also suggested that this change is reversible and limited to the period of ethanol oxidation. 6. It is demonstrated that ethanol-induced triglyceride accumulation is not related to carnitine deficiency.     

Enhancement of antibody synthesis in rats by feeding cis-9,trans-11 conjugated linoleic acid during early life

Previous studies have demonstrated that the intake of a 1% conjugated linoleic acid (CLA) diet in an 80:20 mixture of cis-9,trans-11 and trans-10,cis-12 exerts age-specific effects on the immune system: immunoglobulin enhancement and proliferative down-modulation in neonatal and adult rats, respectively. The present study evaluates the influence of the same diet on antibody synthesis of early infant Wistar rats during suckling and/or after weaning. Dietary supplementation was performed during suckling and early infancy (4 weeks), only during suckling (3 weeks), or only in early infancy (1 week). CLA content in plasma and serum immunoglobulin (Ig) G, IgM and IgA concentration were determined. Proliferation, cytokines and Ig production were evaluated on isolated splenocytes. Cis-9,trans-11- and trans-10,cis-12-CLA isomers were detected in the plasma of all CLA-supplemented animals, and the highest content was quantified in those rats supplemented over the longest period. These rats also exhibited higher concentrations of serum IgG, IgM and IgA. Moreover, splenocytes from CLA-supplemented rats showed the highest IgM and IgG synthesis and interleukin (IL)-6 production, whereas their proliferative ability was lower. In summary, in infant rats, we observed both the enhance antibody synthesis previously reported in neonates, and the reduced lymphoproliferation previously reported in adults.     

Grafting of genetically modified cells: effects of acetylcholine release in vivo.

In this study, microdialysis was used to investigate functional recovery of central cholinergic neurons in the forebrain of rats with cortical devascularizing lesions. Mature male rats were unilaterally lesioned by disruption of the pia arachnoid vessels and genetically modified fibroblasts secreting nerve growth factor (NGF) were placed at the site of the lesion. One month following surgery, microdialysis probes were installed in the remaining cortex and were perfused with artificial cerebrospinal fluid (csf) containing neostigmine (5 nM) and/or KCl (100 mM). The basal (non-stimulated) release of acetylcholine (ACh) in the cortex was similar in all experimental groups, whereas KCl stimulated release of ACh was significantly augmented (P < 0.05) in the ipsilateral remaining cortex in lesioned animals that have been implanted with fibroblasts secreting NGF. These results suggest that NGF secreted by genetically engineered fibroblasts modulates neuroplasticity in the adult mammalian CNS and may favour recovery of cortical function following injury.     

Interaction between morphine and putative excitatory neurotransmitters in cortical neurons in naive and tolerant rats.

Microelectrophoretically applied morphine depressed spontaneously discharging cortical neurones of rats and blocked excitation induced by electrophoretic administrations of either acetylcholine or l-glutamate. This depressant effect and both the anti-acetylcholine and the anti-glutamate effect were naloxone antagonizable and therefore regarded as specific morphine actions. The excitatory effects of morphine were not affected by naloxone application and were classified as non-specific.In chronically morphinized rats the depressant effect of morphine on spontaneous discharge activity and also its blocking action upon acetylcholine and l-glutamate-induced excitation were almost completely abolished. The predominant response in such pre-treated animals was non-specific excitation. Acetylcholine and l-glutamate were found to be more effective in tolerant rats (supersensitivity).     

Partial purification and characterization of an acetylcarnitine hydrolase from bovine epididymal spermatozoa

We previously reported that intact epididymal spermatozoa from bulls and hamsters oxidize [1-14C]acetyl-L-carnitine to 14CO2 at about the same rate as they oxidize [1-14C]acetate. In addition, we showed that acetylcarnitine is hydrolyzed by a hydrolase present in the plasma membrane and that the carnitine moiety does not enter the cell. Here we report the partial purification of the acetylcarnitine hydrolase from bovine spermatozoa and describe some of its properties. The detergent-extracted enzyme was purified by FPLC using an anion-exchange Mono-Q column. The hydrolase activity eluted from the column with the application of 0.22 to 0.30 M NaCl and was separated from acetylcholinesterase activity, which eluted with 0.35 to 0.40 M NaCl. Specific inhibitors of acetylcholinesterase had little effect on acetylcarnitine hydrolase but p-hydroxymercuriphenylsulfonate was a potent inhibitor of the hydrolase. Kinetic studies of the hydrolase yielded a K'm of 6-10 mM for acetylcarnitine and a V'max of 0.16 nmol min-1 mg protein-1. Similar studies with the acetylcholinesterase yielded a K'm for acetylcholine of about 300 microM and a V'max of 165 nmol min-1 mg protein-1. Acetylcarnitine was a poor substrate for the acetylcholinesterase. Several acyl-L-carnitines were tested as substrates for the hydrolase and the preferred substrate was acetylcarnitine. The role of acetylcarnitine hydrolase in the metabolism of acetylcarnitine by epididymal spermatozoa is discussed.     

Corticosteroid regulation of Na+ and K+ transport in the rat distal colon during postnatal development

To study the role of corticosteroids in the regulation of colonic electrogenic amiloride-sensitive Na+ absorption (ISCNa) and barium-sensitive K+ secretion (ISCK) during development, we investigated suckling (10-day old), weanling (25-day old) and adult (90-day old) adrenalectomized rats after they had received aldosterone, dexamethasone or corticosterone. Adrenalectomy reduced markedly ISCNa in suckling rats and completely inhibited ISCNa in weanling animals; the ISCNa was absent in intact adult rats. The doses of aldosterone, corticosterone and dexamethasone estimated to be equivalent to the endogenous production rate of aldosterone and corticosterone restored ISCNa after 1 day in both suckling and weanling rats. Compared with aldosterone, glucocorticoids produced a greater increase in ISCNa. Concurrent spironolactone treatment (a mineralocorticoid antagonist) completely prevented the effect of aldosterone but had no effect in dexamethasone-treated rats. The glucocorticoid antagonist RU 38 486 inhibited the dexamethasone-induction of ISCNa but had no effect on aldosterone. The response to corticosteroids, measured as the increase of ISCNa, declined from suckling to adult rats. In contrast to ISCNa, the same time of treatment and the same doses of corticosteroids did not influence ISCK. ISCK was stimulated only after chronic treatment (4 days). These findings suggest that, in the distal colon of young rats, (1) both corticosteroids may regulate amiloride-sensitive Na+ absorption and barium-sensitive K+ secretion, (2) different receptors mediate the colonic effects of glucocorticoids and mineralocorticoids, (3) immature rats are more sensitive to corticosteroids than adult animals, and (4) the acute effect of corticosteroids is an increase in Na+ absorption which is followed by delayed stimulation of K+ secretion.