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Biomedical subjects

A Arce

Publications and source records attributed to A Arce.

At least 55 records · Page 3Linked to original sources

Effects of cyclosporine at the hypothalamic-pituitary axis in pituitary-grafted young female rats.

This work was designed to investigate the effects of cyclosporine on prolactin secretion by an ectopically grafted heterologous pituitary gland, and on the hypothalamic content of norepinephrine, dopamine and serotonin. The administration of cyclosporine prevented the augmentation in plasma prolactin levels which occurred following an ectopic graft of a litter-mate pituitary gland. In contrast, in sham-operated rats, cyclosporine increased prolactin levels on day 8 of treatment. Both pituitary grafting and cyclosporine treatment in sham-operated rats decreased hypothalamic norepinephrine content. In grafted rats, cyclosporine returned hypothalamic norepinephrine to normal. Hypothalamic serotonin content decreased 8 days after pituitary grafting but increased to the values of control animals after cyclosporine administration. Cyclosporine treatment for 2 and 8 days increased serotonin content in sham-operated animals. As expected, the hypothalamic dihydroxphenylacetic acid/dopamine index increased after pituitary grafting and administration of cyclosporine for 8 days resulted in a further increase. Cyclosporine administration for 2 days, however, decreased this index to the values observed in control animals while drug treatment of control rats for 8 days decreased the dihydroxyphenylacetic acid/dopamine index. In vitro release of prolactin from the ectopic gland was markedly decreased in animals treated with cyclosporine for 2 days and this effect was less evident in 8-day treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Chick imprinting performance and susceptibility to acute stress associated to flunitrazepam receptor increase.

One-day-old chicks were selected on their performance in imprinting behaviour and termed high-imprinted (H-I), partially imprinted (P-I) and low-imprinted (L-I) chicks. Then, H-I and L-I chicks were submitted to acute handling stress and [3H]flunitrazepam receptor-binding was performed on synaptosomal membranes from forebrain at various times after handling. The receptor number significantly increased in L-I but not in H-I chicks at 30 min after handling while the affinity remained unchanged at all times. In addition, when the three selected groups were maintained to reach 15 days of age and then they were submitted to acute swimming stress, the degree of receptor increase was also inversely related to the degree of imprinting performance. The receptor increase associated to swimming stress was higher in the left hemisphere, suggesting an interhemispheric asymmetry of stress effects. The results suggest that more-imprinted chicks are less susceptible than less-imprinted chicks to acute stress associated to central benzodiazepine receptor increase, probably due to differences in the degree of endogenous emotionality.

Animals↗

Acute ethanol administration in diestrus-2 in the rat on pulsatile prolactin and LH release.

Exposure to ethanol is followed by changes in reproductive function in man and animals, characterized by modifications in the secretion patterns of prolactin and luteinizing hormone (LH). As both hormones are secreted in an episodic fashion, the present work was undertaken to study the effects of acute ethanol administration on pulsatile prolactin and LH secretion patterns in adult female rats. Rats were previously cannulated to allow a continuous blood withdrawal to study the pulsatile patterns of prolactin and LH. The mean values of prolactin during the bleeding period and the absolute pulse amplitude of prolactin peaks were significantly increased by acute ethanol administration, whereas a significant decrease of relative pulse amplitude and frequency of this hormone was observed. On the other hand, ethanol administration increased the mean serum LH levels and the absolute and relative amplitudes of LH peaks. Ethanol treatment did not modify either frequency or duration of LH peaks. These data suggest that acute ethanol administration in adult female rats is followed by changes in the pulsatile prolactin and LH secretory patterns, which might be part of the mechanism to explain ethanol effects on the endocrine system.

Animals↗

Piribedil affects dopamine turnover in cochleas stimulated by white noise.

The presence of dopamine (DA) within the cochlea has been previously reported, indicating that its turnover increases under noise stimulation. In the present report, piribedil, a dopaminergic D2 agonist, was used in order to provide evidence of the activity of D2 receptors in the turnover of DA under noise stimulation. Long-Evans rats were intraperitoneally injected with distilled water or with a solution of piribedil one hour previously to either noise or silence exposure. Noise stimulation was performed in an anechoic chamber at 70, 90 or 110 dB SPL for one hour. The animals were then sacrificed and the cochlear contents of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were quantified by HPLC with electrochemical detection. The administration of piribedil to animals kept in silence did not modify the cochlear DA, DOPAC and HVA content. Noise stimulation resulted in a decrease of the cochlear DA content and an increase of the cochlear DOPAC and HVA contents in vehicle treated animals. The administration of piribedil resulted in a blockade of this noise induced cochlear DA turnover. These results suggest that piribedil stimulates cochlear D2 receptors controlling the cochlear DA release. Piribedil action on D2 receptors could explain the improvement observed in some cochleo-vestibular diseases signs after piribedil treatment.

3,4-Dihydroxyphenylacetic Acid↗

Tardive akathisia due to sulpiride.

A 56 year-old woman who suffered from parkinsonism, oro-lingual dyskinesia (OLD) and tardive akathisia (TA) due to sulpiride is reported. OLD and TA appeared after sulpiride withdrawal. The patient was successfully treated with tetrabenazine even a mild parkinsonism was present. TA seems to be related with an apparent dopaminergic hyperactivity and it has to be differentiated of other neuroleptic-induced movement disorders such as restless legs syndrome in order of an appropriate treatment. Sulpiride has the same possible side effects than classic neuroleptics.

Akathisia, Drug-Induced↗

Transient benzodiazepine-GABAA receptor increase after a passive avoidance learning in synaptosomal membranes from chick forebrain.

One-day-old chicks were exposed to a one-time passive avoidance learning task. After chicks peak a bead dipped in a bitter-tasting liquid, they learn to stop pecking the bead. Radioligand binding analysis of [3H]flunitrazepam was performed on crude synaptosomal membranes from forebrains, at 10, 30, and 60 min post-training. Water-trained chicks (control) pecked a bead dipped in water, and they did not learn to stop pecking the bead. The water control was complemented with a methyl anthranilate fed control chick to demonstrate that taste per se does not affect the [3H]flunitrazepam binding. At 30 min in relation to 10 min post-training, the Bmax increased 31% in water-trained chicks and 56% in taste-trained chicks, with Bmax of the taste-trained chicks reaching a value 22% higher than that in water-trained chicks. The difference, attributable to the learning, disappeared at 60 min post-training, and at all times the affinity remained unchanged. The Bmax increase in water-trained chicks might be attributable to psychological stress accompanying the task and the Bmax increase in taste-trained chicks attributable to the learning in addition to the stress accompanying the task. The results suggest that the receptor increase associated with learning is involved in early stages of memory formation.

Animals↗

Thyroid hormones modulate both adenosine transport and adenosine A1 receptors in rat brain.

Adenosine transport and adenosine A1 receptors in rat brain are subjected to regulation by thyroid hormone levels. The studies were carried out with brain stem synaptosomal preparations from rat brain in euthyroid and various hypothyroid situations. The maximum velocity of the nitrobenzylthioinosine (NBTI)-sensitive adenosine transport was 3.3 +/- 0.3 pmol.mg protein-1.s-1 in euthyroid rats. The transport in 1-wk thyroidectomized rats was decreased by 45.8% with respect to controls. No changes were found in the affinity of euthyroid and hypothyroid rats, with the Michaelis-Menten constant values equal to 1.9 +/- 0.9 and 2.0 +/- 0.5 microM, respectively. The transporter number measured by NBTI binding also decreased; the maximum binding capacity (Bmax) was 112.9 +/- 21.9 and 31.3 +/- 4.1 fmol/mg protein for euthyroid and hypothyroid rats, respectively. The adenosine A1 receptors were measured in synaptosomal membrane preparations in the presence of 100 microM guanosine-5'-O-3-thiotriphosphate for cylopenthyl-1,3-dipropylxanthine 8-[dipropyl 2,3-3H(N)] ([3H]DPCPX) binding. In euthyroid rats, the Bmax value was 227.6 +/- 27.6 fmol/mg protein, a significant decrease of 23% was obtained in 1-wk hypothyroid rats. In all other thyroid situations studied, adenosine transport capacity, adenosine transporter number, and adenosine A1 receptor number were restored to control levels.

Adenosine↗

Changes in serum growth hormone and prolactin levels, and in hypothalamic growth hormone-releasing hormone, thyrotropin-releasing hormone and somatostatin content, after superior cervical sympathectomy in rats.

After bilateral superior cervical ganglionectomy (SCGx) of adult male rats, norepinephrine (NE) content of the medial basal hypothalamus (MBH) decreased significantly by 39-47% from 16 h to 7 days after surgery. During this time the levels of serum growth hormone (GH) and prolactin (PRL) and of MBH GH-releasing hormone (GRH), thyrotropin-releasing hormone (TRH) and somatostatin were measured by RIA. In sham-operated controls, serum PRL increased and serum GH decreased 16-24 h after surgery, attaining pre-surgical levels later on. In SCGx rats, significantly lower serum GH and PRL and higher MBH GRH and TRH content as compared to controls was observed 16-24 h after surgery, during the wallerian degeneration phase after SCGx. MBH somatostatin concentration decreased in SCGx rats 20 h after surgery. Two injections of the alpha 1-adrenoceptor blocker prazosin 45 and 90 min before sacrifice, alone or together with the beta-blocker propranolol, prevented the changes in MBH hypophysiotropic hormone content, as well as in serum GH and PRL levels, found in SCGx rats 20 h after surgery. Propranolol treatment did not affect hormone levels. Neither drug modified the decrease in MBH NE content observed after SCGx. The results argue in favor of the existence of physiologically relevant projections from superior cervical ganglion neurons to the MBH controlling hypophysiotropic hormone release.

Animals↗

Effects of noise stimulation on cochlear dopamine metabolism.

Dopamine (DA) appears to be one of the putative neurotransmitters of the lateral efferent olivocochlear fibers. However, its role in the cochlear physiology remains unknown. In this study, animals were exposed for 1 h to white noise at 70, 90 or 110 dB SPL or were kept in silence conditions. Afterwards, the cochlear content of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were analyzed using HPLC coupled to electrochemical detection. Cochlear DA concentration decreased with the noise intensity, while cochlear DOPAC and HVA concentrations increased. Males presented higher cochlear DOPAC contents and lower HVA contents than females. This sexual dimorphism could be related to the link between DA and gonadal steroids. Present results show that DA, as other lateral efferent neurotransmitters, is released and metabolized in relationship with the noise stimulation, and suggest that DA could be involved in the modulation of the type I afferent fiber activity.

3,4-Dihydroxyphenylacetic Acid↗

Benzodiazepine receptor recruitment after acute stress in synaptosomal membranes from forebrain of young chicks: action of Triton X-100.

In young chicks submitted to acute stress by forced swimming there was a significant increase in the number of the measurable [3H]-flunitrazepam receptors in synaptosomal membranes from forebrain. In addition, low subsolubilizing concentrations of Triton X-100 caused a significant increase in the measurable [3H]-flunitrazepam receptor number in synaptosomal membranes from non-stressed chicks. However, this Triton X-100 stimulatory effect was not observed when tested in synaptosomal membranes from stressed chicks. In all cases the affinity remained unchanged. This result suggest that: (i) acute stress and Triton X-100 induce receptor recruitment by enhancing [3H]-flunitrazepam accessibility to a pool of receptors which is unmeasurable either before stress or in absence of detergent; (ii) neither recruitment types are additive and they involve receptors coming from the same nonmeasurable pool; (iii) stress induces a maximal recruitment of existing benzodiazepine receptors; (iiii) the pool of nonmeasurable receptors represents about a quarter of the total in control chicks. The recruitment at a short time of stress could be interpreted in terms involving internalization; recycling or modulation of receptors but not its biosynthesis or degradation.

Acute Disease↗

Determination of the membrane-buffer partition coefficient of flunitrazepam, a lipophilic drug.

The partition coefficient (P) of a benzodiazepine, flunitrazepam (FNTZ), was determined in a synaptosomal membrane/buffer system. A two component model was used, one of the components reflecting the drug partitioning into the membrane, and the other the amount of drug in the aqueous phase retained by the pellet after the centrifugation. The quantity of [3H]FTNZ measured as nonspecifically bound to the membrane includes both components so, the second one had to be discounted and in order to determined its magnitude a parallel experiment was performed using a non-partitioning hydrophilic drug (gamma-[3H]aminobutyric acid, [3H]GABA). The assay required previous determination of the fraction of the total volume of the incubation system that corresponded to membrane (fm). The fm value was calculated from the density value (delta) determined by a picnometer method. The results obtained were: delta = 1.66 +/- 0.02; fm = (1.6 +/- 0.2) 10(-3); P = 18.5 +/- 0.8. This P value could explain nonspecific effects of BZDs on some functions of the neuronal membrane.

Animals↗

GABA interaction with lipids in organic medium.

The interaction of 3H-GABA (gamma-aminobutyric acid and 14C-glutamate with lipids in an aqueous organic partition system was studied. With this partition system 3H-GABA and 14C-glutamate were able to interact with sphingomyelin, sulfatide, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and phosphatidic acid but not with cholesterol or ceramide. In an homogeneous aqueous medium we could not demonstrate any interaction between 3H-GABA and lipids. The apparent dissociation constants (Kd) for 3H-GABA-lipids or 14C-glutamate-lipids interactions in organic medium were in the millimolar range and maximal charge (Bmax) between 3 and 7 moles of GABA or glutamate by mole of lipid. Amino acids such as glutamic acid, beta-alanine and glycine displaced 3H-GABA with the same potency as GABA itself; thus these results show that the interaction lacks pharmacological specificity. To detect this interaction lipid concentrations higher than 2 microM were required and in the partition system 3H-GABA and lipid phosphorus were both concentrated at the interface. Therefore lipids tested with a biphasic partition system do not fulfill the classical criteria for a neurotransmitter receptor at least not for GABA and glutamate.

Amino Acids↗

The biosynthesis of brain gangliosides. Separation of membranes with different ratios of ganglioside sialylating activity to gangliosides.

Brain subcellular fractions were analysed for ganglioside-sialylating activity by measuring the incorporation of N-[3H]acetylneuraminic acid from CMP-N-[3H]acetylneuraminic acid into endogenous ganglioside acceptors (endogenous incorporation) and into exogenous lactosyceramide (haematoside synthetase activity). The ratios of endogenous incorporation to gangliosides and of haematoside synthetase to gangliosides for the synaptosomal and mitochondrial fractions from a washed crude mitochondrial fraction were lower than those obtained for other membrane fractions. The differences appear to reflect intrinsic characteristics of each membrane fraction. The results of labelling in vitro and the time course of labelling of gangliosides of the different subcellular fractions in vivo after injection of N-[3H]acetylmannosamine are consistent with the possibility of a subcellular site for synthesis of gangliosides different from that of ganglioside deposition.

Animals↗