Etienne Comoy

Age-related changes of noradrenergic-NPY interaction in rat brain: norepinephrine, NPY levels and α-adrenoceptors

Abstract Noradrenergic-neuropeptide Y interaction, which is implicated in different physiological functions, was studied in senescent rats. Norepinephrine (NE) and neuropeptide Y (NPY) levels were measured in brainstem and hypothalamus, and α-adrenergic binding was investigated in brainstem in young (4 months) and old (34 months) Wistar rats. NE concentration was the same in senescent rats, whether NPY concentration was decreased both in brainstem and hypothalamus compared to levels in young rats. [ 3 H]prazosin binding to α 1 -adrenoceptors was not modified, but [ 3 H]rauwolscine binding to α 2 -adrenoceptors was altered with age. In fact, the density of α 2 -adrenoceptors( B max ) was lower, while the binding affinity( K d ) was increased in old compared to young rats. These results suggest that the decrease of NPY levels could be one of the possible reasons for changes in [ 3 H]rauwolscine binding to α 2 -adrenoceptors in old rats. The G-protein-adenylate cyclase system, which is impaired in senescent rats, could be involved in the disorganization of noradrenergic-NPY interaction.

Similar pharmacological properties of 8-OH-DPAT and alnespirone (S 20499) at dopamine receptors : comparison with buspirone

Alnespirone (S 20499) has previously been described as a potential anxiolytic drug that acts by stimulation of 5-HT1A receptors. Some data suggest that alnespirone might also be a weak dopamine D2 receptor agonist: it displays moderate affinity for dopamine D2 receptors in vitro and it inhibits prolactin release and induces yawning in rats. In order to test for possible interactions of alnespirone with dopamine receptors in vivo, we studied the changes of in vivo striatal [3H]SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zepine) and [3H]raclopride binding following the injection of a tracer dose of either tritiated ligand (4 microCi) in mice treated with increasing doses of alnespirone (5, 10, 20 and 40 mg/kg, i.p.) and, in the same animals, the changes in the levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). These changes were compared with those produced by increasing doses of the reference 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin, 0.25, 1 and 4 mg/kg, i.p.) or buspirone (5 and 20 mg/kg, i.p.). Decreased in vivo striatal [3H]SCH 23390 specific binding was observed in mice treated with 5, 10 and 40 mg/kg alnespirone. In contrast, increased in vivo striatal [3H]raclopride specific binding was observed in mice treated with 5 and 20 mg/kg alnespirone. In these animals, the striatal 5-HIAA/5-HT ratio was decreased by 5 to 40 mg/kg alnespirone, whereas the striatal HVA/DA ratio was unaffected at all tested doses of alnespirone. Similarly, 8-OH-DPAT decreased specific in vivo striatal [3H]SCH 23390 binding at 0.25, 1 and 4 mg/kg, and increased in vivo specific striatal [3H]raclopride binding at 1 and 4 mg/kg. In the same animals, all tested doses of 8-OH-DPAT decreased the striatal 5-HIAA/5-HT ratio but did not modify the striatal HVA/dopamine ratio. Buspirone (5 and 20 mg/kg) completely inhibited in vivo specific striatal [3H]raclopride binding and increased the striatal HVA/DA ratio but did not modify the striatal 5-HIAA/5-HT ratio, whereas apomorphine (3 mg/kg) decreased both in vivo specific striatal [3H]SCH 23390 and [3H]raclopride binding as well as the striatal HVA/DA and 5-HIAA/5-HT ratios. Finally, increasing doses of alnespirone or 8-OH-DPAT weakly increased sniffing induced by apomorphine (0.75 mg/kg, s.c.) in mice and decreased grooming induced by the dopamine D1 receptor agonist SK&F 39393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol, 1.87 mg/kg, s.c.), whereas buspirone decreased both apomorphine-induced sniffing and SK&F 39393-induced grooming. These results indicate that alnespirone and 8-OH-DPAT have a similar profile and do not seem to interact directly with dopamine receptors. The results also suggest that the stimulation of 5-HT1A receptors by either alnespirone or 8-OH-DPAT modulates the availability of striatal [3H]SCH 23390 and [3H]raclopride binding sites and possibly the functioning of striatal dopamine D1 and D2 receptors in opposite directions.

Stability of epinephrine in alkalinized solutions

STUDY OBJECTIVE Increasing the pH of an epinephrine solution favors its oxidation and may result in a decrease in its biological activity. It is therefore generally assumed that epinephrine and sodium bicarbonate should not be infused in the same IV line during CPR. The aim of this study was to determine the validity of this widely accepted proposition. DESIGN AND SETTING Two different commercial solutions of epinephrine differing only in the concentration of sodium metabisulfite (0.46% and 0.02%) were studied. Two dosages of each solution type (1 mg/1 mL and 10 mg/10 mL) were diluted in 250 mL of 8.4% sodium bicarbonate. MEASUREMENTS AND MAIN RESULTS The concentration of epinephrine was measured at different times for two weeks. It was found that the concentration of epinephrine decreased slowly to zero after two weeks, and was approximately at 70% and 100% of control values at 30 minutes after alkalinization. CONCLUSION It was concluded that epinephrine in an alkaline solution is effectively oxidized but has a slow reaction that may not be clinically relevant over short periods of time.

Changes in brain neuropeptide Y induced by cholecystokinin peptides

Cholecystokinin (CCK) and neuropeptide Y (NPY) are two peptides with opposite effects on the regulation of feeding behaviour. The possible interaction between these two systems has always been controversial. In this study, rat brain NPY levels were assayed after treatment with CCK 8 S and with a potent CCK agonist (Boc-(Nle 28-Nle 31)-CCK 26-33). CCK 8 S and its agonist analogue (50 micrograms/kg i.p.) both decreased hypothalamic and hippocampal NPY levels. This result suggests a negative relationship between NPY and CCK-peptides which is not surprising given their opposite role in the control of feeding. The hypothalamus and secondarily the hippocampus appear to be the site of this interaction; no change in NPY levels was observed in other brain areas (striatum and cortex). The same pattern of variation was found in the plasma, suggesting a direct release from the brain via a mechanism which remains to be investigated. The effect appeared later with the CCK analogue than with CCK 8 S itself; this is not surprising with regard to other behavioural and biochemical effects of the analogue and provides further characterization of its action.

Immunological and enzymatic studies of erythrocytic δ-aminolevulinate dehydratase

SummaryThe δ-aminolevulinate dehydratase (ALA.D) quantitative assay on a centrifugal fast analyser showed that subjects whose blood-lead level varies between 30 and 75 μtg/100 ml (1.5 to 3.75 μM/l) react to blood intoxication by synthesizing de novo an amount of enzyme correlating to blood-lead levels. At higher concentrations, the reactional synthesis occurs very rarely. These results suggest that enzyme is constitutive, but also inductible as soon as its substrate accumulates; this last ability may disappear at high blood-lead levels: a hypothesis is proposed thereafter.

Méthode directe a la diacetylmonoxime pour le dosage de l'urée sanguine

Abstract This paper describes a direct method for the determination of blood urea with diacetylmonoxime-phenazone reagent. Many factors are studied and discussed: concentration of proteins, development and stability of coloration, reproducibility, use of a standard with bovine albumin, etc. This method could also be adapted for automatic systems or in other biological fluids.

Changes in hypothalamic neuropeptide Y concentrations induced by cholecystokinin analogues

Neuropeptide Y (NPY) and cholecystokinin (CCK) are two peptides involved in opposite ways in the control of food intake. A possible interaction between NPY and CCK has not yet been well defined. Two CCK derivatives with agonistic and antagonistic properties were studied with regard to their effects on brain and plasma NPY levels. The CCK agonist decreased NPY levels in plasma and in the hypothalamus but not in the other brain areas assayed. The CCK antagonist reversed the agonist-induced decrease in both plasma and hypothalamus. These results suggest a negative relation between NPY and CCK peptides, which is not surprising given their opposite role in feeding regulation. The hypothalamus, a preferential site of this regulation, appears to be the brain area most involved in the NPY-CCK interaction. The plasma NPY level variations closely reflect the hypothalamic profile, suggesting a direct release of NPY by a mechanism that remains to be investigated.

Stability of adrenaline pH-adjusted solutions of local anaesthetics

Reference books state that increasing the pH of adrenaline (epinephrine) solutions favours their oxidation [l], which becomes significant at pH values above 6 [2]. Thus, during cardiopulmonary resuscitation, bicarbonate and adrenaline are preferably infused in two separate venous lines [3]. Adrenaline is added to local anaesthetics to prolong their duration of action and reduce their systemic toxicity [4]. However, local anaesthetics are weak bases and are prepared commercially in slightly acidic solutions of pH 5-7 [5, 61. To reduce the rate of oxidation of adrenaline in these solutions, a strongly acidic antioxidant, sodium metabisulphite is added [7]. Recent reports have shown that pH-adjustment of local anaesthetics decreases the time to onset of sensory block [8, 93 and increases the duration of the block [8] by increasing the proportion of the non-ionized lipophilic form of the drug. Surprisingly, preliminary reports suggest that although the pH of the solution is increased to 7, the concentration [lo] and biological action [ll] of adrenaline remained constant for at least 2 h. The aim of the present study was to determine adrenaline concentrations over 1 week in pH-adjusted solutions of lignocaine (lidocaine) and bupivacaine. Experimental

Delta aminolevulinic acid dehydratase amounts in lead-exposed subjects: description of a method correlated with the immunoturbidimetric assay

SummaryThe measurement of δ-aminolevulinic acid dehydratase (ALA.D) activity is a good index of lead exposure. Recently, we proposed an immunotubidimetric assay which allows determination of the amount of the enzyme. This last test is particularly interesting for workers presenting high blood-lead levels. We then studied the effects of different agents (dithiothreitol, heat and zinc ions) in restoring the activity of lead-inhibited ALA.D. The individual or combined effects of these three agents showed an additive restoration of activity. The combination of zinc ions with heat and/or DTT gave the best activations, which correlated perfectly with ALA.D amounts. Consequently, the catalytic assay using zinc ions and DTT may be used in routine testing as an indirect measurement of ALA.D amount.

Determinaion de l'acide homoprotocatechique (HPA) urinaire par une methode radio-isotopique

Abstract This paper describes a new radioactive method for estimation of urinary homoprotocatechic acid. This phenolic acid is transformed into labelled homovanillic acid by an enzymatic reaction using catechol- O -methyltransferase and labelled S -adenosyl-methionine. The normal values obtained by this method are found between 406 and 1482 μg/24 h for adults, and between 46 and 229 μg/24 h for children; some results obtained from urine of patients with neuroblastomas and patients with Parkinsons disease given l -Dopa are reported.