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Parenteral nutrients in rat suppresses hepatic vagal afferent signals from portal vein to hypothalamus.

BACKGROUND: Parenteral nutrition (PN) suppresses spontaneous food intake in rats by stimulating dopamine in lateral hypothalamic area (LHA), which is attenuated by vagotomy. Sensors for glucose and for some individual amino acids exist in hepatoportal areas sending signals via hepatic vagal afferents to LHA. Hypothesizing that the decrease in spontaneous food intake occurs because a PN amino acid solution is recognized by portal vein sensors, we measured afferent nerve discharges in hepatic vagus in response to PN. METHODS: Hepatic vagus was divided in 11 rats, and an isolated nerve filament was placed on recording electrodes. Afferent firing rate was recorded before and after injecting during 1 minute a well-balanced crystalline amino acid mixture into either the portal or peripheral vein. Isotonic glucose was used as standard solution. RESULTS: A significant decrease in hepatic vagal afferent discharge rate was recorded after both intraportal and intravenous injection of the PN amino acid mixture. The mean discharge rate was inversely related to the concentration of the solution. Successive injections produced further decreases in discharge rate, and the effect was more sustained. CONCLUSIONS: The observed decrease in discharge rates suggests that the crystalline amino acid PN solution is sensed in hepatoportal areas informing LHA via hepatic afferents. This effect may play a role in regulating food intake during PN.

Afferent Pathways↗

Gastric inhibitory polypeptide and insulin responses to orally administered amino acids in genetically obese hyperglycemic (ob/ob) mice.

The effects of oral administration of eight L-amino acids (alanine, arginine, cysteine, glycine, histidine, hydroxyproline, lysine and threonine) individually or as an amino acid mixture on plasma gastric inhibitory polypeptide (GIP), insulin and glucose concentrations were examined in 18-h fasted obese hyperglycemic (ob/ob) mice. At a dose of 5.4 mmol/kg body weight, arginine, cysteine, histidine and the amino acid mixture were equipotent in terms of increasing plasma GIP and insulin concentrations. Alanine, hydroxyproline and lysine also increased plasma GIP, but insulin concentrations were unchanged. In contrast, threonine failed to affect either GIP or insulin concentrations. There was no correlation between either the incremental or integrated GIP and insulin responses, and none of the amino acids administered affected circulating glucose concentrations. The results indicate that a range of essential and nonessential neutral and basic amino acids stimulate the release of GIP in ob/ob mice. However, GIP made only a modest contribution to the stimulation of insulin secretion following administration of amino acids in the presence of basal glycemia.

Administration, Oral↗

GnRH action in rat anterior pituitary gland: regulation of protein, glycoprotein and LH synthesis.

The effect of synthetic GnRH on the synthesis of proteins and glycoproteins in the anterior pituitary and in vitro release of LH into the medium was studied. A maximal dose (25 ng/ml) of of synthetic GnRH caused optimum release of radioimmunoassayable LH into the medium after 2 h of incubation. A concomitant increase in cyclic AMP accumulation in the tissue and LH in the incubation medium was also observed under the influence of GnRH during different periods of incubation time. Incubation of the rat anterior pituitary with GnRH stimulated the incorporation of [3H] proline into acid precipitable proteins in a time- and dose-dependent manner, similar to radioimmunoassayable LH released into the medium. Similar results were obtained when pituitary was incubated with dibutyryl cyclic AMP. LH, in addition, enhanced the incorporation of [3H] glucosamine and [3H] amino acids mixture into acid-precipitable proteins suggesting that proteins including glycoproteins are synthesized by the rat anterior pituitary under the influence of GnRH. Approximately 10% of the radioactivity associated with proteins comigrated with radioimmunoassayable LH on the gels. GnRH also enhanced the incorporation of [3H] glucosamine and [3H] amino acid mixture into immunoprecipitable LH. The GnRH-induced incorporation of [3H] proline into anterior pituitary proteins was abolished by specific translation inhibitors.

Amino Acids↗

Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals.

RATIONALE: Reduced serotonergic activity has been associated with impulsive behavior; however, intervention studies have been scarce. OBJECTIVES: To examine whether induced lowering of serotonin (5-HT) levels would increase behavioral measures of impulsivity. METHODS: Twenty-four healthy young males ingested a mixture of the essential amino acids except for tryptophan in a balanced, randomized, double-blind, placebo-controlled, cross-over study design. The continuous-performance test-identical pairs was administered when the plasma concentration of tryptophan was expected to be at the lowest point. The plasma concentrations of 23 amino acids were measured at baseline and 5 h after the ingestion of the amino acid mixture. RESULTS: The intervention led to a dramatic fall in free and total plasma tryptophan, and the tryptophan/large neutral amino acids ratio. This in turn has been shown to lower the level of 5-HT in the central nervous system. The tryptophan depletion resulted in a statistically significant more impulsive- or disinhibited response style on the continuous-performance test-identical pairs when the subjects were solving verbal tasks. Depleted subjects exposed to spatial stimuli had fewer correct responses and a decreased ability to discriminate between stimuli. CONCLUSIONS: These results indicate that a rapid lowering of tryptophan increases impulsiveness and decreases discriminating ability in normal individuals. The effect of 5-HT depletion on discriminating ability in this study was similar to that previously reported in depressed patients.

Adult↗

Effect of dietary asparagine and protein-equivalents in crystalline amino acid diets on asparagine metabolism in chicks.

The effect of dietary asparagine and protein-equivalents from crystalline amino acid mixtures upon asparagine metabolism in chicks were studied. Liver and kidney asparaginase activities were significantly increased in chicks fed 44.6% protein-equivalents compared to chicks fed the Illinois chick standard amino acid mixture containing 14.8% protein-equivalents. The asparagine synthetase activity in chick liver and kidney was not significantly changed by protein-equivalents or dietary asparagine. Liver and kidney asparaginase activities in chicks fed 14.8% protein-equivalent standard diets were decreased with increasing levels of dietary asparagine (0,2 and 6%). Kidney asparaginase activities in chicks fed 44.6% protein-equivalents also were decreased with increasing levels of asparagine but liver asparaginase in these chicks was not changed with dietary asparagine. The plasma asparagine concentration was dependent on the amount of dietary asparagine and protein-equivalents. Dietary asparagine increased plasma asparagine in chicks fed 14.8 and 44.6% protein-equivalent diets but plasma asparagine in chicks fed the 14.8% protein-equivalent diet plus 6% asparagine was 3.5 times higher than plasma asparagine in chicks fed the diet containing 44.6% protein-equivalent plus 6% dietary asparagine. Plasma asparagine in chicks fed the 44.6% protein-equivalent diet with 6% asparagine was reduced due to increased asparaginase activity.

Animals↗

THE ISOLATION OF AMINO ACIDS FROM MIXTURES AS THEIR N-2,4-DINITROPHENYL DERIVATIVES, METHIONINE, LEUCINE, PHENYLALANINE, ORNITHINE, LYSINE AND TYROSINE.

1. The separation of the dinitrophenyl derivatives of methionine, leucine (together with isoleucine), phenylalanine, ornithine, lysine and tyrosine from each other, and from the dinitrophenyl derivatives of the other protein amino acids, by partition chromatography on columns is described. 2. The harmful effect on resolving power of using too close-fitting a packing tool in preparing these partition columns is indicated and the dimensions needed to obtain good resolution are given.

Amino Acids↗

The effects of different intravenous feeding regimens on the rates of synthesis of alpha1-antitrypsin after surgery.

The effects of two nutritional regimens on the synthesis of alpha-1 antitrypsin were investigated postoperatively in gynaecological cancer patients. Total parenteral nutrition (TPN) or a hypocaloric amino acid mixture was administered on the day of surgery and continued for 3 days. The rate of synthesis of alpha-1 antitrypsin was estimated by a computer model from serial plasma concentrations of this protein and a reference protein, albumin. The hypocaloric amino acid mixture resulted in a more negative nitrogen balance than that produced during administration of TPN containing the same amount of nitrogen but more non-protein energy. Urinary excretion of 3-methylhistidine was significantly greater (p = 0.017) in the hypocaloric amino acid group (350 +/- 40 mumol/day; mean +/- SE) on the third postoperative day, as compared to the TPN group (240 +/- 20 mumol/day). In spite of this the synthesis of alpha-1 antitrypsin was apparently greater in the hypocaloric amino acid than in the TPN group. The accumulated plasma appearance rate of alpha-1 antitrypsin was significantly higher (p = 0.0465) in HAA group, at 70 h it was 490 +/- 40 compared to 400 +/- 20 times the pre-operative synthesis in the TPN group.

Journal Article↗

Determination of allergenicity to three cow's milk hydrolysates and an amino acid-derived formula in children with cow's milk allergy.

BACKGROUND: Products based on hydrolysed cow milk proteins or amino acid mixtures are recommended in children with cow's milk hypersensitivity. However, some children who are allergic to cow's milk and who clinically react to substitute milk formulas have been observed. OBJECTIVE: To determine the tolerance and allergenicity of protein hydrolysate or amino acid-derived formulas in children with IgE-mediated cow's milk allergy. METHODS: Twenty children with positive cow's milk challenges, positive skin prick tests and/or serum-specific IgE antibodies to cow's milk were selected. Oral challenges, skin prick tests and serum-specific IgE antibodies to extensively hydrolysed whey formula, partially hydrolysed whey formula, extensively hydrolysed casein formula and amino acid-derived formula were performed. RESULTS: Five out of 17 (5/17) children reacted to partially hydrolysed whey formula, (3/16) to extensively hydrolysed whey formula, (2/10) to amino acid-derived formula, (1/16) to extensively hydrolysed casein formula. Only extensively hydrolysed casein formula was tolerated by at least 90% (with 95% confidence intervals) of children. Hydrolysates provoked early and delayed clinical reactions, amino acid mixtures only delayed reactions. Partially hydrolysed whey formula elicited a significantly higher number of positive skin prick test reactions than other formulas. Two children had specific IgE antibodies to extensively hydrolysed whey formula, one to partially hydrolysed whey formula, one to extensively hydrolysed casein formula and none to amino acid-derived formula. CONCLUSION: In this study, none of the cow's milk substitutes has been found to be non-allergenic. Our results suggest that in children with IgE-mediated cow's milk allergy, the first ingestions of extensively hydrolysed cow's milk protein formulas require strict medical supervision because of immediate reactions. This is not the case for amino acid-derived formula. Moreover, our data suggest that treatment of children allergic to cow's milk with cow's milk substitutes should be monitored for several days to document tolerance.

Allergens↗

Serum amino acid concentrations in patients receiving total parenteral nutrition with an amino acid plus dextrose mixture.

The results of monitoring the serum amino acid concentrations during three infusion regimens using a 5:4 mixture of 70% glucose and the synthetic L-amino acid solution, Synthamin 17 (Travasol) are reported. Twelve stabilized patients received continuous total parenteral nutrition (TPN), eight of whom were subsequently placed on a second regimen of cyclical feeding. A separate group of five patients was infused with amino acids, both with and without simultaneous glucose. The serum amino acid concentrations indicated that the supply of valine, leucine, isoleucine, lysine, and histidine, and the synthesis of taurine from the infused methionine was suboptimal, particularly if the period of TPN was prolonged. The synthesis of tyrosine from phenylalanine appeared to be inversely proportional to the infusion rate of the TPN mixture, in particular the glucose component, resulting in depressed tyrosine and increased phenylalanine concentrations in serum during continuous iv nutrition. Cyclical infusions, on the other hand, permitted the tyrosine and phenylalanine concentrations to return to normal during the noninfusion stage of the cycle. Amino acid measurements enabled us to design an amino acids additive mixture which normalized the serum concentrations in three long-term home parenteral nutrition patients. As a result of these investigations serum amino acid measurements are used routinely to monitor the efficacy of TPN and accommodate any specific amino acid requirements of individual patients.

Adult↗

Whole-cell response characteristics of ciliated and microvillous olfactory receptor neurons to amino acids, pheromone candidates and urine in rainbow trout.

Olfactory lamellae of teleosts contain two morphologically different types of olfactory receptor neurons (ORNs): ciliated ORNs (cORNs) and microvillous ORNs (mORNs). However, little is known about the functional difference between these two types of ORNs in fish olfaction. We isolated cORNs and mORNs using a Ca(2+)-free solution method from olfactory organs of the rainbow trout and examined their response characteristics to various odorants including fish pheromone candidates by whole-cell voltage-clamp techniques. Quadruple mixture of amino acids, single amino acids, steroids (analogues of DHP; 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one and ECG; etiocholan-3 alpha-ol-17-one glucuronide), prostaglandins (PGFs) and urine samples collected from immature and mature female fish were applied focally to olfactory cilia or microvilli using a multi-barreled stimulation pipette with a pressure ejection system. Inward current responses to odorants were recorded from both cORNs and mORNs at a holding potential of -60 mV. cORNs responded to the amino acid mixture, single amino acids, urine samples and ECG, whereas mORNs responded specifically either to the amino acid mixture or single amino acids. The response profiles of both cORNs and mORNs to various odorants varied widely. None of cORNs and mORNs responded to fish pheromone candidates, PGFs and DHPs. Androgen treatment of immature fish did not influence olfactory sensitivity of both cORNs and mORNs to the amino acid mixture and both urine samples. Amino acid and bile acid analyses by HPLC showed that both urine samples contained 35 amino acids (1-40 mM) and trace amounts of taurocholic acid and glycoursodeoxycholic acid. Our results suggest that cORNs are 'generalists' that respond to a wide variety of odorants, including pheromones, whereas mORNs are 'specialists', specific to amino acids, and also suggest that PGFs and DHPs are not pheromones for the rainbow trout.

Amino Acids↗

Mood changes following acute tryptophan depletion in healthy adults.

A decrease in central serotonergic activity following plasma tryptophan depletion has been shown to provoke a deterioration of mood. We studied the impact of sex and aggressive traits on mood changes following tryptophan depletion in healthy volunteers. Twelve healthy subjects (6 males, 6 females, 24-31 years), who were screened for psychiatric and non-psychiatric medical illness, were administered a tryptophan-depleting amino acid mixture (TD) and a placebo mixture on two different occasions in a double-blind crossover design. Psychometric measures included the preliminary determination of aggressive traits and depression and repeated assessments of mood and emotionality. The tryptophan-free amino acid mixture caused a marked depletion of plasma tryptophan with lowest levels occurring between 3 and 5 h after TD. Maximum changes in mood occurred about 10 h after TD, but only in high-aggressive women who scored significantly higher in arousal, anger and depressed mood, whereas low-aggressive women and men did not show any effect of TD. In addition, we could not confirm an increase in aggressive mood (anger) after TD in males with higher scores of trait aggression, presumably because the level of trait aggression was not high enough in this group. Due to the small sample size, our results that tryptophan depletion exerts a rapid mood-lowering effect on healthy women with pre-existing aggressive traits can only be seen as preliminary and have to be confirmed in further studies with larger samples.

Adult↗

Effect of high levels of selected dietary essential amino acids on hypercholesterolemia and down-regulation of hepatic LDL receptors in rabbits.

Earlier studies showed that the elevation of serum total and low density lipoprotein (LDL) cholesterol levels produced in rabbits by feeding high levels of a casein amino acid mixture in a cholesterol-free, semipurified diet was due primarily to the essential amino acids (EAA) in the mixture. Replacing all of the non-essential amino acids in the mixture by glutamic acid (45% EAA+Glu) had little effect on the hypercholesterolemia produced by the EAA. Experiments designed to identify the hypercholesterolemic EAA showed that (i) feeding high levels of ketogenic EAA only (45% EketoAA) gave a substantial but variable elevation of serum total and LDL cholesterol and (ii) feeding high levels of all EAA except arginine (45% EAA-Arg) gave a particularly strong hypercholesterolemic response. In rabbits fed the 45% EAA-Arg diet and to a lesser extent, in those fed the 45% EAA+Glu diet, EDTA-sensitive binding of 125I-LDL to hepatic membranes in vitro was reduced compared to a control, low-cholesterolemic group fed all essential and non-essential amino acids at a level corresponding to 14.7% casein, indicating that the hypercholesterolemia was associated with down-regulation of hepatic LDL receptors.

Amino Acids, Essential↗

L-amino acids regulate parathyroid hormone secretion.

Parathyroid hormone (PTH) secretion is acutely regulated by the extracellular Ca(2+)-sensing receptor (CaR). Thus, Ca(2+) ions, and to a lesser extent Mg(2+) ions, have been viewed as the principal physiological regulators of PTH secretion. Herein we show that in physiological concentrations, l-amino acids acutely and reversibly activated the extracellular Ca(2+)-sensing receptor in normal human parathyroid cells and inhibited parathyroid hormone secretion. Individual l-amino acids, especially of the aromatic and aliphatic classes, as well as plasma-like amino acid mixtures, stereoselectively mobilized Ca(2+) ions in normal human parathyroid cells in the presence but not the absence of the CaR agonists, extracellular Ca(2+) (Ca(2+)(o)), or spermine. The order of potency was l-Trp = l-Phe > l-His > l-Ala > l-Glu > l-Arg = l-Leu. CaR-active amino acids also acutely and reversibly suppressed PTH secretion at physiological ionized Ca(2+) concentrations. At a Ca(2+)(o) of 1.1 mm and an amino acid concentration of 1 mm, CaR-active amino acids (l-Phe = l-Trp > l-His = l-Ala), but not CaR-inactive amino acids (l-Leu and l-Arg), stereoselectively suppressed PTH secretion by up to 40%, similar to the effect of raising Ca(2+)(o) to 1.2 mm. A physiologically relevant increase in the -fold concentration of the plasma-like amino acid mixture (from 1x to 2x) also reversibly suppressed PTH secretion in the Ca(2+)(o) concentration range 1.05-1.25 mm. In conclusion, l-amino acids acutely and reversibly activate endogenous CaRs and suppress PTH secretion at physiological concentrations. The results indicate that l-amino acids are physiological regulators of PTH secretion and thus whole body calcium metabolism.

Amino Acids↗

Lowering effect of dietary milk-whey protein v. casein on plasma and liver cholesterol concentrations in rats.

The effect of dietary whey protein v. casein on plasma and liver cholesterol concentrations was investigated in female, weanling rats. Balanced, purified diets containing either whey protein or casein, or the amino acid mixtures simulating these proteins, were used. The high-cholesterol diets (10 g cholesterol/kg feed) had either 150 or 300 g protein or amino acids/kg feed. The diets were fed for 3 weeks. At the low dietary protein level, whey protein v. casein did not affect plasma total cholesterol, but lowered the concentration of liver cholesterol. At the high dietary protein level, whey protein significantly lowered plasma and liver cholesterol and also plasma triacylglycerols. The hypocholesterolaemic effect of whey protein was associated with a decrease in very-low-density-lipoprotein cholesterol. At the high dietary protein concentration, whey protein reduced the faecal excretion of bile acids when compared with casein. The effects of intact whey protein v. casein were not reproduced by the amino acid mixtures simulating these proteins. It is suggested tentatively that the cholesterol-lowering effect of whey protein in rats is caused by inhibition of hepatic cholesterol synthesis.

Animals↗

Comparative effects of protein, protein hydrolysate and amino acid diets on nitrogen metabolism of normal, protein-deficient, gastrectomized or hepatectomized rats.

The effects of diets containing protein, protein hydrolysate or an amino acid mixture on nitrogen metabolism of normal and severely protein-deficient rats and on rats after gastrectomy and hepatectomy were compared. In experiment 1, rats weighing about 80 g were fed one of three experimental diets containing casein, protein hydrolysate or an amino acid mixture for 28 d. In experiment 2, rats weighing about 270 g were fed a protein-free diet for 40 d, and then one of the above three experimental diets for 14 d. In experiment 3, rats weighing about 220 g were totally gastrectomized and fed one of the three experimental diets for 21 d. In experiment 4, rats weighing about 210 g had about 70% of the liver resected, and then were fed one of the three experimental diets for 15 d. In all four experiments, daily food intake, daily body weight gain, nitrogen balance, urinary nitrogen compounds, body composition and hematologic values were measured. In normal, protein-deficient and hepatectomized rats, most results were similar for the groups fed protein, protein hydrolysate or amino acid diets, except that urinary ammonia was higher in the group fed the amino acid diet than in the other two groups. For about 10 d after total gastrectomy, food intake and growth of the animals fed the protein diet were lower than in the other two groups.

Amino Acids↗

Hyperglycemia after protein ingestion concurrent with injection of a GLP-1 receptor agonist in rats: a possible role for dietary peptides.

Protein ingestion after injection of the glucagon-like peptide-1 receptor agonist Exendin-4 (Ex-4) causes hyperglycemia in rats. The objectives of this study were to determine the components of protein digestion responsible for this effect and to associate it with changes in the concentrations of other metabolites and hormones. Two experiments were conducted. In the first experiment, food-deprived rats were gavaged with intact whey (WP) or albumin protein, their hydrolysates, amino acid mixtures (1 g/2.5 ml), or water 5 min after injection of either PBS or Ex-4 (0.5 microg/rat). Tail vein blood was analyzed for glucose over 2 h. In the second experiment, food-deprived rats were gavaged with WP with or without Ex-4. Groups of conscious rats were killed by decapitation either before, or at selected times after gavage. Plasma concentrations of glucose, amino acids, free fatty acids (FFA), glycerol, insulin, glucagon, and leptin were measured. In experiment 1, blood glucose was higher when intact proteins and protein hydrolysates, but not amino acid mixtures, were given with than without Ex-4 (P < 0.05). In experiment 2, concentrations of glucose, FFA, and the ratio of tyrosine to branched-chain amino acid were higher (P < 0.01), but leptin and essential amino acid concentrations were lower (P < 0.05), and insulin, glucagon, and glycerol were similar when WP was given with or without Ex-4. We conclude that the hyperglycemia caused by the administration of Ex-4 concurrently with dietary protein arises from the action of peptides released during digestion and their interaction with Ex-4 in the regulation of glucose, fatty acid, and amino acid metabolism.

Amino Acids↗

Reduction of paraquat-induced oxidative stress in rats by dietary soy peptide.

The effect of a dietary soy protein isolate (SPI), soy peptide (PEP) and the amino acids in soy protein on paraquat (PQ)-induced oxidative stress was investigated in rats. In the first experiment, male Wistar rats were fed on experimental diets containing casein (CAS), SPI and PEP as nitrogen sources with or without 0.025% PQ. The reduced food intake and body weight gain of the rats fed with PQ was mitigated by either the SPI or PEP intake. Both SPI and PEP prevented the elevation of the serum TBARS concentration and tended to prevent the elevation of lung weight induced by PQ. In the second experiment, the rats were fed on diets containing an amino acid mixture resembling casein (CASAA) or soy protein (SPIAA) with or without PQ. The SPIAA intake did not affect the reduction of food intake and body weight gain, nor the elevation of lung weight and TBARS in the serum and liver induced by PQ. These results demonstrate that the intake of either dietary SPI or PEP, but not an amino acid mixture resembling soy protein, had the effect of reducing PQ-induced oxidative stress in rats.

Amino Acids↗

The contribution of a Ca(2+)-activated Cl(-) conductance to amino-acid-induced inward current responses of ciliated olfactory neurons of the rainbow trout.

To determine whether amino-acid-induced inward currents of ciliated olfactory receptor neurons (ORNs) in rainbow trout (Oncorhynchus mykiss) include a Ca(2+)-activated Cl(-) conductance, we first studied changes in reversal potential and the current/voltage relationships of the responses of ORNs to an amino acid mixture (l-alanine, l-arginine, l-glutamate and l-norvaline; all 10 mmol l(-)(1)) with different concentrations of Na(+) and Cl(-) in the perfusion and recording pipette solutions. We also examined the effects of six different Cl(-) channel blockers on the responses of ORNs using a conventional whole-cell voltage-clamp technique. The amino acid mixture and one blocker were applied focally to the cilia of ORNs using a double-barrelled micropipette and a pressure ejection system. The expected shifts in reversal potential, indicating the contribution of the Ca(2+)-activated Cl(-) conductance, occurred in both positive and negative directions depending on the external and internal Na(+) and Cl(-) concentrations. Niflumic acid, flufenamic acid, NPPB [5-nitro-2-(3-phenylpropylamino)-benzonate] and DCDPC (3', 5-dichlorodiphenylamine-2-carboxylate), at 0.5 mmol l(-)(1), reversibly blocked both the amino-acid-induced inward currents and the background activity in most ORNs. The effectiveness of these blocking agents varied from 77 to 91 % for ORNs perfused externally with standard Ringer's solution. SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate), at 5.0 mmol l(-)(1), irreversibly inhibited the physiological response (100 % inhibition), whereas DIDS (4,4'-diisothiocyanatostilbene-2, 2'-disulphonate), at 5.0 mmol l(-)(1), had the smallest effect (45 %) of the inhibitors tested. The dose of niflumic acid inducing 50 % inhibition (IC(50)), determined specifically for the current component of the Ca(2+)-activated Cl(-) channels, was 70 micromol l(-)(1). Our results suggest that these blockers are not specific for Ca(2+)-activated Cl(-) channels and that the density of these channels varies between individual ORNs. Our results also show that the Ca(2+)-activated Cl(-) conductance plays an important role in olfactory transduction and allows fishes to adapt to various ionic environments.

Amino Acids↗