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Biomedical subjects

J A Angulo

Publications and source records attributed to J A Angulo.

17 recordsLinked to original sources
PubMed1992

Quantitative in situ hybridization evidence for differential regulation of proenkephalin and dopamine D2 receptor mRNA levels in the rat striatum: effects of unilateral intrastriatal injections of 6-hydroxydopamine.

Nigrostriatal (NS) dopaminergic (DA) neurons are thought to exert an inhibitory influence on striatal enkephalinergic systems through their DA D2 receptors. In order to investigate the effects of partial lesions of the NS DA on striatal proenkephalin (PEK) and D2 receptor mRNAs, animals were allocated to High, Intermediate, and Low rotators on the basis of amphetamine-induced rotation observed after intrastriatal injections of 6-hydroxydopamine (6-OHDA). On the ipsilateral side of the lesions, there were significant increases in PEK mRNA in the total aspect of the caudate-putamen (CPu) of the High (+204%), the Intermediate (+125%), and of the Low (+67%) rotation groups in comparison to controls; these changes correlated positively with increases in rotation rate. Unexpectedly, there were also significant increases in striatal PEK mRNA on the contralateral side although these changes were much less prominent than those observed on the side of the lesions. Conversely, only the High rotation group showed significant increases (+112%) in D2 receptor mRNA which occurred only on the lesioned side. Interestingly, the low rotation group actually showed some non-significant decreases (-25%) on the side of the lesions. These results indicate that partial lesions of the NS DA projections are sufficient to cause substantial increases in PEK mRNA but not in D2 receptor mRNA. These data also provide evidence that the two nigrostriatal DA projections and the systems which they modulate might be under interdependent sets of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Involvement of dopamine D1 and D2 receptors in the regulation of proenkephalin mRNA abundance in the striatum and accumbens of the rat brain.

The effects of short-term treatment (6 h) with selective D1 or D2 agonists and antagonists on the mRNA for proenkephalin in the medial and anterior aspects of the caudate-putamen and the nucleus accumbens were assessed by in situ hybridization histochemistry. Proenkephalin mRNA abundance was significantly changed in the striatum and accumbens in response to D2 receptor manipulation. D2 blockade with haloperidol or raclopride increased, whereas D2 stimulation with LY-171555 (D2 agonist) decreased, striatal and accumbens proenkephalin mRNA abundance. Antagonism of D1 receptor activity with SCH-23390 significantly decreased proenkephalin mRNA abundance in all brain regions. Concurrent administration of the D1 agonist SKF-38393 prevented the SCH-23390 effect in all brain areas. The data demonstrate that acute treatment with dopaminergic D2 agonists and antagonists affects proenkephalin mRNA abundance in the striatum and accumbens via a D2 receptor mechanism, consistent with the concept that D2 receptor function inhibits the synthesis of the mRNA encoding the enkephalin peptides. Moreover, D1 receptor activity, directly or indirectly, exerts modulatory effects on proenkephalin mRNA abundance in the striatum and nucleus accumbens.

Animals↗
PubMed1991

Chronic treatment with pentazocine or SFK 10047 decrease proenkephalin mRNA levels in the rat striatum and nucleus accumbens.

In order to assess the effect of sigma (sigma) receptor activity on striatal and limbic enkephalinergic cells we measured proenkephalin mRNA levels by in situ hybridization histochemistry after chronic treatment with the sigma-receptor agonist drugs SKF 10047 or pentazocine. Chronic treatment with SKF 10047 decreased proenkephalin mRNA levels in the anterior aspect of the caudate-putamen (CPU) and the nucleus accumbens by 20-22% relative to controls. No significant effect was observed in the medial aspect of the CPU. Treatment with pentazocine decreased proenkephalin mRNA levels by 20-25% in all 3 brain regions. The results demonstrate that sigma-receptor activity can exert tonic effects on proenkephalin mRNA expression in the striatum and the nucleus accumbens of the rat.

Animals↗
PubMed1991

Effects of deoxycorticosterone treatment on beta-subunit mRNA for (Na + K)ATPase in brain regions determined by in situ hybridization.

1. We have used in situ hybridization techniques to determine the mRNA for (Na + K)ATPase in 20 brain regions from control rats and rats treated with high doses of deoxycorticosterone (DOC). 2. DOC-treated rats developed a salt appetite following the second hormone administration on alternate days and were used after the fourth DOC administration. 3. DOC treatment did not change the number of silver grains/cell deposited in cells from Ca1, CA2, CA3, and CA4 hippocampal subfields, dentate gyrus, cerebral cortex, medial preoptic area (POA), substantia nigra, and periventricular gray matter. 4. Nonsignificant reductions were detected in lateral POA, medial and lateral septum, caudate-putamen, and three amygdaloid nuclei (cortical, basolateral, and central) from DOC-treated rats. 5. Significant reductions were obtained, after DOC administration, in arcuate and ventromedial hypothalamic nuclei and medial and lateral amygdala. 6. The results suggested that regulation of the beta-subunit mRNA of (Na + K)-ATPase may be related to the central actions of mineralocorticoids in the control of salt intake.

Animals↗
PubMed1991

Surgery for gastroesophageal reflux in children with normal pH studies.

Esophageal pH monitoring is recognized as the best diagnostic procedure for gastroesophageal reflux (GER) and operation is seldom recommended in the absence of abnormal pH data. To emphasize that operation should not be ruled out for children who may have false-negative pH studies, we report 14 patients operated on for GER in spite of normal pH-monitoring. The mean age was 54 months (range, 18 to 90). Clinical features included vomiting, dysphagia, respiratory disease, anemia, and torticollis. All had radiologic evidence of GER, and 10 had endoscopic and histological esophagitis. Conventional pH-monitoring values were normal but lower esophageal sphincter pressure and propulsive peristalsis were significantly decreased whereas nonpropulsive contractions were predominant. Operation was recommended after an average of 24 months of unsuccessful medical treatment. Independent postoperative assessment showed that 13 of the 14 patients were relieved of their symptoms and dysphagia persists in one. We suggest that the diagnosis of GER should be accepted on the basis of sound clinical judgement plus more than one abnormal test even when pH results are normal. Operation should not be withheld when clinically indicated. There are several explanations for false-negative pH studies, of which alkaline reflux is probably the most important and warrants further investigation in children.

Child, Preschool↗
PubMed1991

Isolation stress increases tyrosine hydroxylase mRNA in the locus coeruleus and midbrain and decreases proenkephalin mRNA in the striatum and nucleus accumbens.

Isolation of adult animals represents a form of psychological stress from which the animals cannot escape. In order to assess the effect of this stressor on neurochemical substrates in the brain, we assessed behavior and measured tyrosine hydroxylase and proenkephalin mRNA levels in selected brain areas by in situ hybridization histochemistry. Tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (LC) were significantly and progressively increased by 18, 42 and 68% after 7, 14 or 28 days of isolation, respectively. TH mRNA in the midbrain was transiently increased by isolation. Levels were significantly elevated by 34 and 48% above group-housed controls in the ventral tegmentum and the substantia nigra, respectively, after 14 days of isolation. In the forebrain, proenkephalin (PE) mRNA levels were found to be transiently decreased by 29% in the anterior and medial aspects of the caudate-putamen and the nucleus accumbens after 7 or 14 days of isolation stress, but the levels returned toward control levels after 28 days of isolation. Behavioral tests indicate that isolated animals progressively became more aggressive with duration of stress and showed a small but significant decrease in locomotor activity. The results demonstrate that a physically noninvasive stressor such as isolation of adult male rats can produce significant alterations in brain neurochemistry. The neurochemical responses observed may represent a brain mechanism designed to help the organism adapt to or protect from the deleterious effects of chronic psychological stress.

Animals↗
PubMed1991

Regulation by dopaminergic neurotransmission of dopamine D2 mRNA and receptor levels in the striatum and nucleus accumbens of the rat.

The effect of dopamine depletion or pharmacological blockade of dopamine receptors on striatal and accumbens dopamine D2 mRNA and receptor levels was assessed by in situ hybridization histochemistry and receptor autoradiography. The time course of pharmacological blockade with haloperidol demonstrates a complex mode of regulation of dopamine D2 mRNA and receptor levels. By day 8 of haloperidol treatment, D2 mRNA and receptor levels were decreased (up to 20%) in the medial and anterior aspects of the caudate-putamen (mCPU and aCPU) and the nucleus accumbens (NAc). However, by day 21 of haloperidol treatment, D2 mRNA and receptor were increased relative to vehicle-injected controls. Likewise, unilateral dopamine depletion due to 6-hydroxydopamine (6-OHDA) lesions of mesencephalic dopaminergic neurons resulted in decreased levels of D2 receptor mRNA by day 8 post-lesion in the ipsilateral mCPU, aCPU and the NAc. However, at days 14 or 21 post-lesion, there was a reversal of the effect with increases of up to 22% in all brain regions ipsilateral to the lesion. Although no decreases in receptor level were observed at day 8, significant increases in receptor level in all three brain regions were detected at days 14 and 21 post-lesion. The results demonstrate that midbrain dopaminergic innervation exerts tonic effects on the levels of dopamine D2 receptor and mRNA in the caudate-putamen and the nucleus accumbens of the rat. Changes in receptor level are frequently accompanied by comparable changes in mRNA level, indicating a mass action relationship between receptor level and receptor biosynthesis in these forebrain regions in the rat.

Animals↗
PubMed1991

Intrastriatal implants of fetal mesencephalic cells attenuate the increases in striatal proenkephalin mRNA observed after unilateral 6-hydroxydopamine-induced lesions of the striatum.

Unilateral injections of 6-hydroxydopamine (6-OHDA) cause significant bilateral increases in striatal proenkephalin (PEK) mRNA in rat brain. We have tested the possibility that implantation of fetal mesencephalic cells can normalize these changes. Two types of grafts were used: 1) embryonic day-15 mesencephalic cells and 2) embryonic day-15 cells which have been modified with a retroviral vector containing a cDNA for protein kinase C (PKC). At two months after grafting, both cell types cause significant attenuation of the increases which occurred on the side of the lesion. However, only the PKC-modified cells cause normalization of the changes on the contralateral side. These observations indicate that, in addition to normalizing supersensitive striatal dopamine (DA) D2 receptors, embryonic cells can also attenuate the alterations in PEK mRNA observed after lesions of the nigrostriatal DA system. The finding that the PKC-modified cells caused bilateral effects in the striatum suggests that second messenger systems may play a role in the bilateral improvement reported in parkinsonian patients who had gotten unilateral intrastriatal transplants.

Animals↗
PubMed1991

Genomic effects of cold and isolation stress on magnocellular vasopressin mRNA-containing cells in the hypothalamus of the rat.

We assessed the effects of cold and isolation stress on arginine vasopressin (AVP) mRNA in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Vasopressin mRNA levels were determined by in situ hybridization histochemistry at the cellular level. In posterior magnocellular neurons of the PVN isolation stress for 7 or 14 days increased vasopressin mRNA levels 28 and 29%, respectively, compared to group-housed controls. No significant alterations in vasopressin gene expression were observed in the SON after 7 or 14 days of isolation stress. Scattered magnocellular AVP mRNA-expressing cells of the medial parvocellular PVN showed increases of 19 and 34% after 7 and 14 days of isolation, respectively. We also studied the effect of cold or combined cold and isolation stress on vasopressin gene expression in the PVN and SON. Cold stress for 3 h daily for 4 consecutive days increased AVP mRNA levels in the posterior magnocellular PVN by 15%. Cold-isolated animals showed an increase of 21%. No significant effect on AVP mRNA levels in the SON was observed. In contrast to the posterior magnocellular PVN, cold or cold-isolation stress increased AVP mRNA in magnocellular neurons of the medial parvocellular region of the PVN by 25 and 43%, respectively, relative to control rats. These results suggest that psychological and metabolic stress may be added to the list of stressors that activate the hypothalamo-neurohypophysial system.

Animals↗
PubMed1991

Brain and liver angiotensinogen messenger RNA in genetic hypertensive and normotensive rats.

The brain's renin-angiotensin system in integrally involved in the regulation of blood pressure and fluid/mineral metabolism. Enhanced activity of the angiotensin system in the brain has been implicated as a possible source of the hypertension and the elevated salt appetite of the spontaneously hypertensive rat, as compared with the Wistar-Kyoto rat. This study tested whether these inbred strains of hypertensive and normotensive rats differ in central or peripheral expression of the gene coding for angiotensinogen, the prohormone for the angiotensin peptides. Angiotensinogen messenger RNA was measured in the brain by in situ hybridization and in the liver by Northern blot analysis, using a synthetic oligonucleotide. There was a 28% greater expression of the angiotensinogen gene in the region of the anteroventral hypothalamus, preoptic area, and medial septum of the hypertensive strain. There were no differences between strains in liver angiotensinogen gene expression. These results are consistent with the possibility that enhanced elaboration of the angiotensin prohormone in the brain contributes, in part, to the hypertension or the elevated salt appetite of the spontaneously hypertensive rat.

Angiotensinogen↗
PubMed1990

Effect of typical and atypical neuroleptic treatment on protachykinin mRNA levels in the striatum of the rat.

A significant population of striatal neurons synthesize the tachykinin peptides substance P and neurokinin A. The synthesis of these neuropeptides is under tonic stimulation by dopaminergic neurotransmission. Since typical and atypical neuroleptic drugs display differential effects on the activity of dopaminergic neurons, we evaluated the effect of typical (haloperidol and prolixin) and atypical (molindone, thioridazine and chlozapine) chronic neuroleptic treatment on protachykinin mRNA levels in the medial aspect of the caudate-putamen by in situ hybridization histochemistry. Both typical and atypical neuroleptics decreased protachykinin mRNA levels by 22-40% relative to saline-injected controls. Clozapine failed to affect protachykinin mRNA levels. The data suggest the hypothesis that decreased striatal protachykinin mRNA levels may not be directly linked to development of extrapyramidal side effects.

Animals↗
PubMed1990

Sigma receptor blockade by BMY 14802 affects enkephalinergic and tachykinin cells differentially in the striatum of the rat.

We determined proenkephalin and protachykinin mRNA levels in the striatum of the rat by in situ hybridization histochemistry in controls and in animals treated for 14 days with the potential neuroleptic drug BMY 14802 (15 mg/kg i.p.). Proenkephalin mRNA levels were increased relative to control values by 107, 88 and 94% and protachykinin mRNA levels decreased by 17, 28 and 10% in the rostral, medial and caudal aspects of the caudate-putamen, respectively. The data suggest that sigma receptor activity, directly or indirectly, affects proenkephalin and protachykinin mRNA expression in striatal neurons.

Animals↗
PubMed1990

Nerve growth factor (NGF) potentiates the changes in striatal proenkephalin mRNAs subsequent to 6-hydroxydopamine-induced lesions of the substantia nigra.

The topographical changes in proenkephalin (PEK) mRNAs which occur in the caudate-putamen (CPu) after 6-hydroxydopamine (6-OHDA)-induced unilateral lesion of the mesostriatal dopamine (DA) pathway were evaluated by quantitative in situ hybridization. These lesions caused significant increases in PEK mRNA in all regions of the caudate-putamen (CPu). The chronic intraventricular administration of NGF potentiated the increases in PEK mRNA, with the magnitude of changes being greater in the dorsomedial and dorsolateral regions of the striatum. NGF did not affect the loss of tyrosine hydroxylase mRNA observed in the substantia nigra ipsilateral to the 6-OHDA-induced lesion. These results demonstrate that alterations which occur in a neuropeptide system as a consequence to 6-OHDA-induced denervation of the striatum can respond to NGF administration in a topographical fashion.

Animals↗
PubMed1990

Effect of chronic typical and atypical neuroleptic treatment on proenkephalin mRNA levels in the striatum and nucleus accumbens of the rat.

We measured proenkephalin (PEK) mRNA levels in the anterior and medial aspects of the caudate-putamen (CPU) and in the nucleus accumbens (NAc) of the rat by in situ hybridization histochemistry after chronic treatment for 21 days with typical (haloperidol and prolixin) and atypical (molindone, thioridazine, and clozapine) neuroleptics. Chronic administration with these drugs resulted in PEK mRNA levels that were 60-80% higher than controls in the anterior and medial aspects of the CPU but only 25-30% over controls in the NAc. All three atypical neuroleptics studied increased PEK mRNA in the following order: anterior-CPU, thioridazine greater than clozapine and molindone; medial-CPU, thioridazine and molindone greater than clozapine; and NAc, thioridazine much greater than molindone and clozapine. Chronic treatment with the specific dopamine D2 antagonist sulpiride also caused elevation in PEK mRNA levels in all three brain regions studied whereas the specific serotonin S2 receptor blocker, cinanserin, had no significant effects on PEK mRNA levels. These results are consistent with the hypothesis that elevated levels of the enkephalins in the mesolimbic system may be necessary for antipsychotic activity. They also support the idea that the undesirable motoric signs and symptoms observed after chronic treatment with typical neuroleptics may not be the result of increased levels of enkephalins in the basal ganglia because atypical neuroleptics which are almost totally devoid of these side effects caused similar increases in PEK mRNA in the CPU.

Animals↗
PubMed1985

Effect of deoxyribopolymers and ribopolymers on the sensitivity of the cyclic-AMP receptor protein of Escherichia coli to proteolytic attack.

The cAMP receptor protein (CRP) is an allosteric protein in which binding of cAMP effects a conformational change with a consequent increased affinity for DNA. Unliganded CRP is relatively resistant to attack by a variety of proteases (trypsin, subtilisin, Staphylococcus aureus V8 protease, clostripain, chymotrypsin) which cleave cAMP-CRP, producing N-terminal cores which have lost DNA binding activity. Binding of double-stranded deoxyribopolynucleotides and calf thymus DNA by cAMP-CRP confers protection against attack by trypsin, subtilisin, S. aureus V8 protease, and clostripain. Such cAMP-CRP-DNA complexes remain sensitive to attack by chymotrypsin. Of the single-stranded deoxy- and ribopolynucleotides tested, only r(I)n and r(A)n gave significant protection against attack by these proteases (with the exception of chymotrypsin). Since the cutting sites for trypsin (Lys 130) and subtilisin (Leu 116) are not part of the C-terminal DNA binding domain, it would appear that binding of DNA may confer conformational changes on other regions of cAMP-CRP.

Bacterial Proteins↗