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J Pineda

Publications and source records attributed to J Pineda.

At least 37 records · Page 2Linked to original sources
PubMed1998

Somatodendritic alpha2-adrenoceptors in the locus coeruleus are involved in the in vivo modulation of cortical noradrenaline release by the antidepressant desipramine.

The effect of the antidepressant and selective noradrenaline reuptake blocker desipramine (DMI) on noradrenergic transmission was evaluated in vivo by dual-probe microdialysis. DMI (1, 3, and 10 mg/kg, i.p.) dose-dependently increased extracellular levels of noradrenaline (NA) in the locus coeruleus (LC) area. In the cingulate cortex (Cg), DMI (3 and 10 mg/kg, i.p.) also increased NA dialysate, but at the lowest dose (1 mg/kg, i.p.) it decreased NA levels. When the alpha2-adrenoceptor antagonist RX821002 (1 microM) was perfused in the LC, DMI (1 mg/kg, i.p.) no longer decreased but rather increased NA dialysate in the Cg. In electrophysiological experiments, DMI (1 mg/kg, i.p.) inhibited the firing activity of LC neurons by a mechanism reversed by RX821002. Local DMI (0.01-100 microM) into the LC increased concentration-dependently NA levels in the LC and simultaneously decreased NA levels in the Cg. This decrease was abolished by local RX821002 administration into the LC. The results demonstrate in vivo that DMI inhibits NA reuptake at somatodendritic and nerve terminal levels of noradrenergic cells. The increased NA dialysate in the LC inhibits noradrenergic activity, which in part counteracts the effects of DMI on the Cg. The modulation of cortical NA release by activity of DMI at the somatodendritic level is mediated through alpha2-adrenoceptors located in the LC.

Adrenergic alpha-Antagonists↗
PubMed1998

Development of gastric slow waves in preterm infants measured by electrogastrography.

The aim of this study was to investigate the developmental process of gastric myoelectrical activity (GMA) in preterm infants. Nineteen healthy preterm infants were studied. GMA was recorded using surface electrogastrography, and six follow-up studies were performed in each subject. Spectral analysis methods were applied to compute the parameters of the electrogastrogram (EGG). The results showed that there was a developmental process of GMA with age during the first 6 mo of life. 1) The percentage of normal slow waves showed a progressive increase after birth (36.7 +/- 6.1, 37.8 +/- 6.2, 47.0 +/- 10.0, 52.2 +/- 12.2, 55.2 +/- 9.7, and 65.8 +/- 13.5% at 1 and 2 wk and 1, 2, 4, and 6 mo, respectively); 2) there was a significant postprandial increase in the percentage of normal slow waves during the first 2 mo after birth; and 3) the percentages of normal slow waves for different gestation ages were not statistically significant. In conclusion, the percentage of normal slow waves is low at birth and there is a developmental process that may be stimulated by enteral feeding.

Electromyography↗
PubMed1997

CREB (cAMP response element-binding protein) in the locus coeruleus: biochemical, physiological, and behavioral evidence for a role in opiate dependence.

Chronic morphine administration increases levels of adenylyl cyclase and cAMP-dependent protein kinase (PKA) activity in the locus coeruleus (LC), which contributes to the severalfold activation of LC neurons that occurs during opiate withdrawal. A role for the transcription factor cAMP response element-binding protein (CREB) in mediating the opiate-induced upregulation of the cAMP pathway has been suggested, but direct evidence is lacking. In the present study, we first demonstrated that the morphine-induced increases in adenylyl cyclase and PKA activity in the LC are associated with selective increases in levels of immunoreactivity of types I and VIII adenylyl cyclase and of the catalytic and type II regulatory subunits of PKA. We next used antisense oligonucleotides directed against CREB to study the role of this transcription factor in mediating these effects. Infusion (5 d) of CREB antisense oligonucleotide directly into the LC significantly reduced levels of CREB immunoreactivity. This effect was sequence-specific and not associated with detectable toxicity. CREB antisense oligonucleotide infusions completely blocked the morphine-induced upregulation of type VIII adenylyl cyclase but not of PKA. The infusions also blocked the morphine-induced upregulation of tyrosine hydroxylase but not of Gialpha, two other proteins induced in the LC by chronic morphine treatment. Electrophysiological studies revealed that intra-LC antisense oligonucleotide infusions completely prevented the morphine-induced increase in spontaneous firing rates of LC neurons in brain slices. This blockade was completely reversed by addition of 8-bromo-cAMP (which activates PKA) but not by addition of forskolin (which activates adenylyl cyclase). Intra-LC infusions of CREB antisense oligonucleotide also reduced the development of physical dependence to opiates, based on attenuation of opiate withdrawal. Together, these findings provide the first direct evidence that CREB mediates the morphine-induced upregulation of specific components of the cAMP pathway in the LC that contribute to physical opiate dependence.

Adenylyl Cyclases↗
PubMed1997

Carbon dioxide regulates the tonic activity of locus coeruleus neurons by modulating a proton- and polyamine-sensitive inward rectifier potassium current.

The electrophysiological effects of CO2 on locus coeruleus noradrenergic neurons were investigated in rat brain slices. Under control conditions, when slices were perfused with artificial cerebrospinal fluid containing 24 mM NaHCO3/5% CO2 (pH approximately 7.34, 33 degrees C) and exposed to 5% CO2/95% O2 arriving through an interface chamber, locus coeruleus neurons discharged spontaneously at approximately 1 Hz. Extracellular recordings showed that lowering CO2 that arrived through the chamber below 5% resulted in reductions in firing rate, often with a complete cessation of activity when exogenous CO2 was removed completely. Intracellular recordings revealed that lowering CO2 produced an outward current with an increase in slope conductance and a reversal potential near the potassium equilibrium potential; doubling the concentration of external potassium shifted the reversal potential of the current activated by CO2 removal by approximately +20 mV. Raising CO2 above 5% induced an increase in firing rate, an inward current, a decreased slope conductance at potentials near resting membrane voltage, and an increased slope conductance at more negative potentials. These effects of CO2 were mimicked by other manipulations that are known to affect intracellular pH. For example, NH4Cl, which acutely induces intracellular alkalinization, caused a marked reduction in firing rate, an outward current and an increased slope conductance that reversed near the potassium equilibrium potential. Bath-applied barium blocked the effects induced by removal of CO2 or addition of NH4Cl. The polyamine spermine (tetrahydrochloride) applied via intracellular micropipettes blocked the outward current induced by removal of CO2 or addition of NH4Cl. Spermine (free base) or an equivalent concentration of putrescine failed to alter the CO2 (0%)- or NH4Cl-induced effects. We conclude that CO2 maintains the tonic activity of locus coeruleus neurons by decreasing intracellular pH which, in turn, closes inward rectifier potassium channels, an effect that may be mediated by a protonated polyamine. According to this model, when there is alkalinization of locus coeruleus cells through removal of CO2 or addition of NH4Cl, endogenous spermine or a similar polyamine becomes partially deprotonated, releasing the channel block and allowing the cell to hyperpolarize. The possible implications of these results for the physiological effects of CO2 in the locus coeruleus are discussed.

Ammonium Chloride↗
PubMed1997

Enhanced alpha2A-autoreceptor reserve for clonidine induced by reserpine and cholinomimetic agents in the rat vas deferens.

1. The adaptive changes in the functional parameters of the presynaptic alpha2A-adrenoceptors in rat vas deferens were examined after treatments with the monoamine depleter reserpine or with the direct/indirect cholinomimetic agents pilocarpine and neostigmine. 2. For this purpose, we studied the inhibition induced by the alpha2-adrenoceptor agonist clonidine on the twitch contraction of the vas deferens elicited by electrical field stimulation, in animals that had been treated with acute (single dose), short-term (for 4 days) and chronic (for 11 days) regimens of reserpine (0.25 mg kg(-1), s.c., every 48 h), pilocarpine (10 mg kg(-1), i.p., every 12 h) or neostigmine (0.1 mg kg(-1), i.p., every 12 h). The irreversible receptor alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 300 nM) was used to block partially the alpha2A-adrenoceptor-mediated effect of clonidine. 3. In control (untreated) animals, clonidine inhibited concentration-dependently the twitch response of the vas deferens (pEC50 = 8.66) with a maximal effect near 100%. The apparent affinity constant for clonidine was estimated with the nested hyperbolic methodology (pK(A) = 7.10). The analysis of the occupancy-effect relation for clonidine revealed a large receptor reserve at alpha2A-adrenoceptors. 4. Acute, short-term and chronic treatments with reserpine increased the sensitivity of alpha2A-adrenoceptors to clonidine (decreased the EC50) by about 3, 4 and 9 fold, respectively, and also increased the pool of receptor reserve for this agonist (decreased the K(E)) by 4, 10 and 10 fold, respectively. Receptor affinity values were not changed after treatments. 5. Short-term and chronic, but not acute, treatments with pilocarpine and neostigmine increased the sensitivity of alpha2A-adrenoceptors to clonidine (decreased the EC50) by about 3 and 2 fold, respectively, and also increased the pool of receptor reserve for this agonist (decreased the K(E)) by 2 and 3 fold, respectively. Receptor affinity values were not changed after these treatments. 6. These results indicate that an enhancement of the receptor reserve for clonidine might account for the supersensitivity of alpha2A-adrenoceptors induced by reserpine, pilocarpine or neostigmine treatments in the rat vas deferens.

Adrenergic alpha-Agonists↗
PubMed1997

Receptor reserve and turnover of alpha-2 adrenoceptors that mediate the clonidine-induced inhibition of rat locus coeruleus neurons in vivo.

The population of reserve alpha-2 adrenoceptors that mediate the inhibitory effect of clonidine on the activity of locus coeruleus neurons has been studied using extracellular recordings in anesthetized rats. Animals were pretreated with the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1-2-dihydroquinoline (EEDQ). In rats pretreated with EEDQ (1, 2 and 6 mg/kg, i.p., 6 hr before experiment), there was an increase in firing rate, a reduction in firing regularity (i.e., increased variation coefficient) and an increase in burst firing of locus coeruleus neurons. Partial receptor inactivation with EEDQ (1 and 2 mg/kg, i.p.) caused a dose-dependent shift to the right of dose-effect curves for i.v. administered clonidine together with a reduction in its maximal effect. Higher doses of EEDQ (6 mg/kg, i.p.) completely abolished the effect induced by clonidine. This blockade was associated with a progressive decrease in the number of remaining receptors (noninactivated receptors). The pseudo-constant of dissociation for the drug-receptor complex was calculated to be approximately 70 micrograms/kg. The receptor occupancy-effect relationship was hyperbolic giving a value of only approximately 4% occupancy at 50% maximal effect. Estimates of noninactivated receptors and percentage of receptor occupancy at 50% of maximal effect were comparable when locally administered clonidine was used. After complete receptor inactivation with EEDQ (6 mg/kg), dose-effect curves for clonidine recovered gradually. The inhibitory effect of clonidine returned faster (half-life = 14 hr) than the receptor pool (half-life = 37 hr). These results indicate that locus coeruleus neurons have a large reserve of alpha 2 adrenoceptors that in addition, are rapidly turned over.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1996

Effect of oxytocin on growth hormone release in vitro.

The effect of oxytocin (OT) on growth hormone (GH) secretion was investigated using dispersed rat anterior pituitary cells. OT dose-dependently inhibited GH secretion as well as GHRH-stimulated GH release. The inhibitory actions of OT on GH release were totally abolished by pretreatment with the OT-antagonist VAP 259. The peptides galanin and cholecystokinin did not affect the OT-induced inhibition on basal or GHRH-stimulated GH release. Several possible mechanisms by which OT may influence GH release are discussed.

Animals↗
PubMed1996

Agmatine does not have activity at alpha 2-adrenoceptors which modulate the firing rate of locus coeruleus neurones: an electrophysiological study in rat.

Agmatine (decarboxylated arginine) has been proposed as an endogenous ligand for non-adrenoceptor, imidazoline binding sites, but also binds to alpha 2-adrenoceptors. The interaction of agmatine with alpha 2-adrenoceptors was evaluated by studying the effect of agmatine on the firing rate of locus coeruleus (LC) neurones using extracellular recordings in anesthetized rats and rat brain slices. In vivo, local application of agmatine into the LC caused a slight and short-lasting increase in cell firing rate (P < 0.005). In vitro, agmatine failed to change the firing rate of LC neurones nor did it antagonize the inhibitory effect of noradrenaline on these cells. Since alpha 2-adrenoceptors are known to inhibit the firing of LC cells, we conclude that agmatine does not have agonist or antagonist properties at alpha 2-adrenoceptors of these neurones.

Agmatine↗
PubMed1996

Nitric oxide and carbon monoxide activate locus coeruleus neurons through a cGMP-dependent protein kinase: involvement of a nonselective cationic channel.

Nitric oxide (NO) and carbon monoxide (CO) have been identified as two diffusible signaling messengers in the brain, capable of stimulating soluble guanylate cyclase. Locus coeruleus (LC) is rich in the alpha 1 and beta 1 subunits of soluble guanylate cyclase. Therefore, the possible role of the cGMP pathway in the regulation of LC neurons was investigated with electrophysiological techniques in rat brain slices. Bath application of various NO donors or CO-containing solutions increased the firing rate of most LC neurons. This activation was reversed by the NO scavenger hemoglobin, but not by methemoglobin. Bath or intracellular application of selective activators of cGMP-dependent protein kinase also caused increases in LC cell firing rate. The actions of NO donors and kinase activators were mutually occlusive and reversed by H8, an inhibitor of the cGMP-dependent protein kinase. Hemoglobin and H8 reduced the firing rate of LC neurons, but no change was found with inhibitors or activators of the NO synthase. In intracellular and whole-cell recordings, NO effect was associated with an inward current and an increase in the input conductance (mean reversal potential = -27 mV); these effects were abolished using a low-sodium buffer. Spontaneous EPSCs of LC cells were not modified with the NO donor administration. Taken together, these data suggest that NO and CO activate noradrenergic neurons of LC via a cGMP-dependent protein kinase and a nonselective cationic channel. It also is proposed that these effects occur at the postsynaptic level and that there may be a tonic regulation of LC neuronal firing by the cGMP pathway.

Animals↗
PubMed1996

Regulation of hypothalamic somatostatin, growth hormone-releasing hormone, and growth hormone receptor messenger ribonucleic acid by glucocorticoids.

Although it is well known that chronic treatment with glucocorticoids inhibits somatic growth, the mechanism of action of this inhibitory effect is not completely understood. It is likely that glucocorticoids act at various levels, including pituitary, hypothalamus, and peripheral organs modulating GH synthesis, secretion, and action. In this work, we evaluated the effect of dexamethasone on hypothalamic somatostatin and GH-releasing hormone (GHRH) messenger RNA (mRNA) levels by in situ hybridization. We found a significant decrease of somatostatin mRNA content in the periventricular nucleus of the hypothalamus after 3, 8, and 15 days of treatment with dexamethasone. Furthermore, we observed a reduction in GHRH mRNA levels in the arcuate nucleus after 8 and 15 days of treatment with this steroid. As it has been shown that GH feeds back to regulate somatostatin and GHRH expression at the hypothalamic level through high affinity GH receptors, we evaluated the possibility of a GH-mediated action in the inhibitory effect of glucocorticoids on somatostatin and GHRH mRNA levels. To address this issue, we first studied the GH receptor mRNA content in both the periventricular and arcuate nuclei of the hypothalamus after dexamethasone treatment. Secondly, the effect of dexamethasone on somatostatin and GHRH mRNA levels in hypophysectomized animals also was assessed. We found a significant decrease in GH receptor mRNA levels in the periventricular nucleus and in the arcuate nucleus after 1, 3, 8, and 15 days of glucocorticoid administration. Finally, in hypophysectomized rats, dexamethasone treatment for 15 days did not reduce somatostatin mRNA levels in the periventricular nucleus but significantly decreased GHRH mRNA content in the arcuate nucleus. In summary, our results suggest an inhibitory GH-mediated effect of dexamethasone on somatostatin mRNA levels in the periventricular nucleus and an inhibitory direct effect of dexamethasone on GHRH neurones in the arcuate nucleus.

Animals↗
PubMed1996

N400-like potentials elicited by faces and knowledge inhibition.

Within the theoretical framework of reference, the brain errs in processing complex stimuli, such as faces. Thus, these stimuli not only activate accurate representations but also inaccurate representations corresponding to known persons who resemble the face stimulus, and hence knowledge about these known persons. Since more errors are made in processing unfamiliar than familiar stimuli, these inaccurate activations are assumed to be more frequent, and/or more intense, with unknown than with known faces. Moreover, top-down mechanisms favor representations of stimuli that are congruent with the context, and representations of known persons, even if inaccurate, receive an additional amount of activation in contexts wherein known faces are expected. Inaccurate representations have to be inhibited to achieve accurate recognition. Thus, more inhibition would be required for unknown than for known faces, and in contexts wherein known faces are expected. The aim of the present work is to study the hypothesis that the N400 component of the event-related potentials (ERPs) reflects the inhibition of knowledge, and to see whether this hypothesis accounts for the N400-like potential elicited by faces. To achieve that goal, ERPs to known and unknown faces were recorded while the richness in known faces of each experimental block, and thus the expectancy for known faces, was manipulated. Consistent with the hypothesis, the amplitudes of the N400-like components were greater in conditions where more inhibition was required, i.e. for unknown rather than for known faces, and in the context of the block rich in known faces. This context effect was larger for unknown than for faces, and in the context of the block rich in known faces. This context effect was larger for unknown than for known faces.

Adult↗
PubMed1996

Role of glucocorticoids in the neuroregulation of growth hormone secretion.

Elevated glucocorticoid (GC) levels produce a marked impairment in somatic growth in both rodents and primates. In addition, GC play an important role in the regulation of growth hormone (GH) synthesis and secretion. Blunted GH response to stimulation tests in conditions of chronic exposure to excessive cortisol secretion or administration are well documented. In contrast, acute administration of GC to normal human subjects induces a transient increase in plasma GH levels. This dual action of GC on GH secretion is probably due to the fact that they act at different loci; i.e. in the regulation of GH transcription and GHRH and somatostatin receptors at the pituitary level as well as GHRH, somatostatin and GH receptor gene expression at the hypothalamic level.

Animals↗
PubMed1995

The stimulatory effect of clonidine through imidazoline receptors on locus coeruleus noradrenergic neurones is mediated by excitatory amino acids and modulated by serotonin.

Clonidine and other imidazoline/oxazoline drugs, such as cirazoline and rilmenidine, have been shown to stimulate the activity of noradrenergic neurones in the locus coeruleus (NA-LC) by an alpha 2-adrenoceptor-independent mechanism through the activation of I-imidazoline receptors. The endogenous modulation of the stimulatory effect of clonidine on NA-LC neurones was further investigated after inactivation of alpha 2-adrenoceptors with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). In EEDQ-pretreated rats (6 mg/kg, i.p., 6 h), clonidine caused a rapid and dose-dependent (320-5120 micrograms/kg, i.v.) increase in the firing rate of NA-LC neurones (ED50 = 809 micrograms/kg, Emax = 90%). The stimulatory effect of clonidine on NA-LC neurones was completely blocked by pretreatment of rats with the excitatory amino acid receptor antagonist kynurenic acid (1-3 mumol in 10-30 microliters, i.c.v., 2-5 min before clonidine). In contrast, the stimulatory effect of clonidine on NA-LC neurones was potentiated by pretreatment with reserpine (5 mg/kg, s.c., 18 h) (Emax increased by 63%). Pretreatment with alpha-methyl-p-tyrosine (250 mg/kg, i.p., 24 h) did not alter the stimulatory effect of clonidine, but pretreatment with p-chloro-phenylalanine (400 mg/kg, i.p., 24 h) markedly enhanced the stimulatory effect of clonidine on NA-LC neurones (Emax increased by 139%). The present results indicate that the imidazoline receptor-mediated stimulatory effect of clonidine on NA-LC neurones is an indirect effect dependent on an excitatory amino acid pathway and modulated by an inhibitory serotonin mechanism.

Adrenergic alpha-Antagonists↗
PubMed1995

Hypogonadotrophic hypogonadism with hyposmia, X-linked ichthyosis, and renal malformation syndrome.

OBJECTIVE: The aim of this study was the endocrinological, enzymatic, and genetic evaluation of a family with a complex syndrome associating hypogonadotrophic hypogonadism with hyposmia, X-linked ichthyosis and renal malformation. DESIGN: Hypothalamic-pituitary-testicular function, olfaction, steroid sulphatase activity, and morphological renal studies were assessed. DNA molecular analyses were carried out in all the patients. PATIENTS: Two brothers and their maternal uncle showed the clinical picture of congenital ichthyosis, hypogonadism, hyposmia and unilateral renal maldevelopment. MEASUREMENTS: LH and FSH were determined by RIA basally and after GnRH stimulation, and the test repeated after a period of GnRH priming. Testosterone response to hCG was measured. Arylsulphatase C assay was performed as a measure of steroid sulphatase activity. DNA amplification analysis and Southern blot analysis of four Xp22.3 loci were performed. RESULTS: Low levels of gonadotophins, basally and after acute GnRH, increased clearly after GnRH priming. Low testosterone levels increased promptly after hCG. Subnormal levels of arylsulphatase C were detected. Hyposmia and renal hypoplasia or aplasia were demonstrated. A large Xp 22.3 deletion including the genes responsible for X-linked ichthyosis (steroid sulphatase deficiency) and Kallmann syndrome was demonstrated. CONCLUSIONS: The absence of the gene encoding steroid sulphatase accounts for the X-linked ichthyosis in these patients, whereas the absence of the Kallmann syndrome gene accounts for hypogonadism, anosmia and for the single kidney found in two of the three patients.

Adolescent↗
PubMed1994

Decreased growth hormone response to dexamethasone stimulation test in obese children.

Acute administration of glucocorticoids is a recently described stimulus for growth hormone secretion. The aim of the present study was the assessment of dexamethasone-induced growth hormone secretion in obese children. Dexamethasone iv tests were carried out in 14 normal control and 8 obese children. Growth hormone was measured by radioimmunoassay up to 5 h after dexamethasone administration. Dexamethasone elicited clear growth hormone secretion in normal children (mean peak 12.3 +/- 1.6; area under the curve 682.3 +/- 74.3). In the obese children, dexamethasone induced a slight but significant (p < 0.01) increase in growth hormone over basal values. However, the growth hormone response in this group was significantly lower than in the normal controls, when comparing both mean peak (5.5 +/- 2.3, mean +/- SEM) (p < 0.01) and area under the curve (306.8 +/- 44.5) (p < 0.001).

Adolescent↗