Search PubMed⌕ Search

Biomedical subjects

A J Bean

Publications and source records attributed to A J Bean.

At least 37 records · Page 2Linked to original sources
PubMed1992

Cloning of human neurotensin/neuromedin N genomic sequences and expression in the ventral mesencephalon of schizophrenics and age/sex matched controls.

A human genomic clone encompassing exons 1-3 of the neurotensin/neuromedin N gene was identified using a canine neurotensin complementary DNA probe. Sequence comparisons revealed that the 120-amino acid portion of the precursor sequence encoded by exons 1-3 is 89% identical to previously determined cow and dog sequences and that the proximal 250 bp of 5' flanking sequences are strikingly conserved between rat and human. The 5' flanking sequence contains cis-regulatory sites required for the induction of neurotensin/neuromedin N gene expression in PC12 cells, including AP1 sites and two cyclic adenosine-5'-monophosphate response elements. Oligonucleotide probes based on the human sequence were used to examine the distribution of neurotensin/neuromedin N messenger RNA in the ventral mesencephalon of schizophrenics and age- and sex-matched controls. Neurotensin/neuromedin N messenger RNA was observed in ventral mesencephalic cells some of which also contained melanin pigment or tyrosine hydroxylase messenger RNA. Neurons expressing neurotensin/neuromedin N messenger RNA were observed in the ventral mesencephalon of both schizophrenic and non-schizophrenic humans.

Adult↗
PubMed1992

Differential expression of acidic and basic FGF in the rat substantia nigra during development.

Both acidic (aFGF) and basic (bFGF) fibroblast growth factors have been shown to be present in the adult rat ventral mesencephalon and to exert effects on cultured mesencephalic cells. In the present study we have examined the expression of aFGF and bFGF in the rat ventral mesencephalon at various stages of development. bFGF was present at all ages examined [embryonic day 16 (E16) to postnatal day 90 (P90)]. In contrast, aFGF was not detectable at embryonic and early postnatal ages, but was observed at later (P20, P60, P90) postnatal stages. These data suggest that aFGF and bFGF may have functions in mesencephalic dopamine neurones in different stages of development.

Aging↗
PubMed1991

Effect of intracerebral injection of monoclonal acetylcholinesterase antibodies on cholinergic nerve terminals in the rat central nervous system.

In the rat, unilateral intrastriatal injection of monoclonal antibodies to acetylcholinesterase (AChE) produced ipsilateral disappearance of AChE-positive nerve terminals within striatum and adjacent cortex. No alterations in striatal staining patterns were observed for tyrosine hydroxylase, somatostatin, neuropeptide Y, substance P, or neurotensin. Ultrastructural studies demonstrated the presence of degenerating AChE-positive boutons ipsilaterally, while tyrosine hydroxylase positive terminals seemed unaffected. Apomorphine administration to rats which had received unilateral antibody injection resulted in ipsilateral rotational behavior. These data suggest that selective effects on cholinergic terminals with functional deficits can be produced within the central nervous system by intracerebral injection of AChE antibodies.

Acetylcholinesterase↗
PubMed1991

Expression of acidic and basic fibroblast growth factors in the substantia nigra of rat, monkey, and human.

The distribution of acidic (aFGF) and basic (bFGF) fibroblast growth factor mRNA and protein were examined in mesencephalon by immunohistochemistry, immunoblot analysis, in situ hybridization histochemistry, and RNA analysis. Coexistence of aFGF or bFGF with tyrosine hydroxylase protein in nigral cells was observed with immunohistochemistry. Both aFGF and bFGF mRNAs were found in the substantia nigra. Unilateral 6-hydroxydopamine lesions of nigrostriatal neurons resulted in a loss of aFGF and tyrosine hydroxylase [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] mRNA-positive neurons on the lesioned side. The distribution of aFGF mRNA in monkey brain was similar to that seen in the rat. RNA and immunoblot analysis confirmed the presence of both aFGF and bFGF mRNAs and proteins in the substantia nigra of rat, monkey, and human.

Animals↗
PubMed1991

Effects of haloperidol administration on in vivo extracellular dopamine in striatum and prefrontal cortex after partial dopamine lesions.

The effects of haloperidol on striatal and prefrontal cortical extracellular fluid dopamine (DA) concentrations were examined in sham-operated control rats and in rats which had received partial lesions of their dopamine systems. In control rats haloperidol administration produced increases in extracellular fluid DA concentrations in both the striatum and prefrontal cortex. However, in rats which had been partially lesioned with intracerebroventricular 6-hydroxydopamine, haloperidol produced an increase in extracellular fluid DA concentration in the prefrontal cortex but failed to alter striatal DA release. These data suggest that nigrostriatal and mesocortical DA neurons have different response capabilities following partial DA lesions.

Animals↗
PubMed1991

Extracellular dopamine and neurotensin in rat prefrontal cortex in vivo: effects of median forebrain bundle stimulation frequency, stimulation pattern, and dopamine autoreceptors.

In vivo microdialysis coupled with HPLC and radioimmuno-assay techniques were used to analyze dopamine (DA) and neurotensin (NT) in prefrontal cortical extracellular fluid following electrical stimulation of mesocortical axons. The release (overflow into the extracellular fluid) of both DA and NT increased with increasing number of impulses and with frequency. At the lowest frequency tested (2.5 Hz), DA release was significantly increased, while there was no significant increase in the release of NT. As the frequency of stimulation was increased from 2.5 to 20 Hz, the ratio of extracellular DA:NT decreased exponentially. Stimulation in a burst pattern produced greater release of both DA and NT than tonic stimulation when the number of impulses per second and the total number of impulses were held constant. Furthermore, blockade of DA autoreceptors with sulpiride stereoselectively increased the release of DA while decreasing the release of NT. These data suggest that the release of coexistent molecules (DA and NT) from mesocortical neurons can be influenced by physiological and pharmacological factors such that under certain conditions simultaneous or differential release may occur.

Animals↗
PubMed1990

Effects of dopamine autoreceptor stimulation on the release of colocalized transmitters: in vivo release of dopamine and neurotensin from rat prefrontal cortex.

The in vivo release of dopamine and neurotensin from the rat medial prefrontal cortex was studied using perfusion microdialysis coupled with sensitive radioimmunoassay and HPLC techniques. Following stimulation of dopamine autoreceptors with either apomorphine (30 micrograms/kg, s.c.) or EMD-23448 (10 microM in the perfusion buffer) a decrease in dopamine and an increase in neurotensin release was observed. The release of both substances was measured in the same dialysis sample. These data suggest that activation of dopamine autoreceptors in the prefrontal cortex produces opposing effects on the release of dopamine and neurotensin.

Animals↗
PubMed1989

Stimulation-induced release of coexistent transmitters in the prefrontal cortex: an in vivo microdialysis study of dopamine and neurotensin release.

Extracellular fluid levels of dopamine and neurotensin in the rat prefrontal cortex were measured using in vivo microdialysis. Electrical stimulation of the median forebrain bundle resulted in increased release of both dopamine and neurotensin from the prefrontal cortex. Thus, stimulation of neurons in which dopamine and neurotensin are colocalized can evoke the in vivo release of both substances.

Animals↗
PubMed1989

Effects of dopamine depletion on striatal neurotensin: biochemical and immunohistochemical studies.

Interactions between striatal dopamine (DA) and neurotensin (NT) have been suggested by anatomical, behavioral, and biochemical studies. Nigrostriatal DA neurons, in contrast to mesocorticolimbic DA neurons, do not appear to contain NT. Thus, distinct neuronal elements subserve interactions between DA and NT within the striatum. We have previously demonstrated that reserpine-induced depletion of striatal DA is accompanied by a dose- and time-dependent increase in striatal NT concentrations. In order to further characterize the effects of reserpine and to define the mechanism by which reserpine acts to increase striatal NT concentrations, we have used immunohistochemical and biochemical approaches. Immunohistochemical examination of rats pretreated with reserpine revealed marked increases in the density of NT-like immunoreactive (NT-li) perikarya and fibers, and the development of NT-li patches. Pretreatment with reserpine had no apparent effect on NT synthesis, as assessed by examination of cycloheximide-induced inhibition of protein synthesis. However, reserpine administration resulted in a significant decrease in the release of both DA and NT into the striatal extracellular fluid, as measured by in vivo microdialysis. These data suggest that the increase in striatal NT concentrations observed after reserpine treatment results from decreased release, rather than increased synthesis of the peptide.

Animals↗
PubMed1989

Dopamine and neurotensin storage in colocalized and noncolocalized neuronal populations.

The effects of reserpine on dopamine (DA) and neurotensin (NT) levels were studied in four different brain regions of the rat. Reserpine (0.5-5.0 mg/kg i.p., 6, 18, 48 and 72 hr) produced a dose- and time-dependent decrease in both DA and NT levels in the prefrontal cortex, a brain region innervated by a mixed DA/NT projection. The effect of reserpine was not mimicked by alpha-methylparatyrosine (200 mg/kg i.p.) pretreatment. Furthermore, the reserpine-induced decline in prefrontal cortex DA and NT levels occurred after gamma-butyrolactone (GBL)-induced inhibition of impulse flow (750 mg/kg i.p.). In contrast, in the nucleus accumbens and striatum, regions which contain colocalized (nucleus accumbens) and intrinsic (striatum and nucleus accumbens) neurotensin perikarya, reserpine produced declines in DA and increases in NT levels. alpha-Methylparatyrosine decreased striatal and nucleus accumbens DA levels without altering NT levels in these structures. GBL produced an increase in DA levels in the nucleus accumbens and striatum while decreasing nucleus accumbens and striatal NT levels. Reserpine attenuated the decline in nucleus accumbens and striatal NT levels produced by GBL. In the periaqueductal grey, a brain region densely innervated by NT which has a small population of DA perikarya, reserpine had no effect on NT levels. Because there is no known colocalization of DA and NT in the striatum, the increases in striatal NT levels after depletion of DA may indicate that striatal DA afferents control the release and/or synthesis of NT within NT cells in the striatum, thus leading to alterations in striatal tissue levels.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Butyrolactone↗
PubMed1988

Regulation of A8 dopamine neurons by somatostatin.

The effects of depletion of somatostatin in the region of the retrorubral field on in vivo tyrosine hydroxylation in the A8 cell group were assessed. Local injections of cysteamine into the central amygdaloid nucleus, source of a somatostatin input to the A8 cell group region, or directly into the retrorubral field resulted in an increase in in vivo tyrosine hydroxylation in the A8 cell group. Levels of somatostatin-like immunoreactivity in the retrorubral field were decreased by approximately 50% by the cysteamine treatment. These data suggest that somatostatin may hold A8 dopamine neurons under tonic inhibition.

Amygdala↗
PubMed1988

Re-evaluation of histidyl-proline diketopiperazine [cyclo(His-Pro)] effects on food intake in the rat.

Histidyl-proline diketopiperazine [cyclo(His-Pro)], a metabolite of thyrotropin releasing hormone (TRH), has been reported to decrease food intake of rats in a variety of feeding models following intracerebroventricular (ICV) injection. We have re-evaluated the anorectic effects of cyclo(His-Pro) on food deprivation-induced and spontaneous feeding. When injected ICV at the end of the light period into ad lib fed rats, neither the naturally occurring cyclo(L-His-L-Pro) isomer (14 to 1000 nmole/rat) nor any of the four cyclo(D,L-His-D,L-Pro) stereoisomers (100 nmole/rat) significantly suppressed food intake at any hour for up to 12- or 24-hr post-injection. Bombesin (0.6 nmole/rat ICV) decreased food intake in the same model by up to 86% with anorexia still apparent 15-hr post-injection (71%, p less than 0.001). In two food deprivation-induced feeding models, cyclo(L-His-L-Pro) (100 and 1000 nmole/rat ICV) did not cause anorexia while TRH (10 and 1000 nmole/rat ICV) maximally suppressed food intake by 74% (p less than 0.02) and 50% (p less than 0.01). Occasional transient increases of food consumption were observed in cyclo(His-Pro)-treated rats during both spontaneous and induced feeding. Cyclo(L-His-L-Pro) was also without effect on food intake when intraperitoneally administered at 12.5 and 30 mumole/kg to schedule fed rats. TRH at 30 mumole/kg IP transiently suppressed food intake of schedule fed rats (p less than 0.005). These findings indicate that cyclo(His-Pro) does not exhibit anorectic activity in the rat and cast doubt on the concept that TRH-induced anorexia results from conversion of TRH to an active cyclo(His-Pro) metabolite.

Animals↗
PubMed1988

The effects of pertussis toxin on autoreceptor-mediated inhibition of dopamine synthesis in the rat striatum.

Activation of synthesis-modulating dopamine autoreceptors by dopamine or its agonists has been shown to inhibit dopamine synthesis in the rat striatum. However, systemic administration of the direct-acting dopamine agonist apomorphine failed to inhibit dopamine synthesis in striata from rats that had received local unilateral administration of pertussis toxin. Apomorphine did reduce dopamine synthesis by greater than 50% in sham injected control rats as well as in the striata opposite to the side of pertussis toxin injection. Examination of G proteins in striatal tissue revealed that 61% of the G proteins were ADP-ribosylated in vivo by direct pertussis toxin injection. These data suggest that guanine nucleotide regulatory proteins mediate the effects of activation of striatal synthesis-modulating dopamine autoreceptors.

4-Butyrolactone↗
PubMed1987

Stress-induced alterations in neurotensin, somatostatin and corticotropin-releasing factor in mesotelencephalic dopamine system regions.

The effects of exposure to acute mild footshock stress on concentrations of neurotensin-, somatostatin-, and corticotropin-releasing factor-like immunoreactivity (li) in mesotelencephalic dopamine system regions of the rat were examined. Mild stress exposure resulted in a selective and regionally specific increase in neurotensin-li concentrations in the ventral tegmental area (VTA), source of the dopaminergic innervation of the mesocortical and mesolimbic dopaminergic terminal fields. Concentrations of somatostatin- or corticotropin-releasing factor-li were not changed in any area examined. Levels of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid, were increased only in the VTA and medial prefrontal cortex. These data suggest that neurotensin in the VTA may be involved in environmentally elicited activation of certain mesotelencephalic dopamine neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Chronic proglumide increases [3H]spiperone binding in the rat brain.

The cholecystokinin (CCK) antagonist, proglumide, administered chronically (41.0-53.5 mg/kg per day, 14 days) to rats via osmotic mini-pumps, produced a significant 13% increase in the number of [3H]spiperone labeled binding sites (Bmax) in the striatum. There was no associated change in the affinity (Kd) of [3H]spiperone for the striatal binding sites. Given chronically at lower dose levels (10.4-13.6 or 21.8-29.8 mg/kg per day), or acutely in doses of 10, 20 or 40 mg/kg s.c., proglumide failed to alter the binding of [3H]spiperone to rat striatal tissue. These data indicate long-term proglumide administration increases the number of binding sites for [3H]spiperone, thought to be a ligand for dopamine D-2 receptors.

Animals↗
PubMed1984

[D-Arg]Kyotorphin-induced ipsilateral rotation: evidence for in vivo effects independent of Met-enkephalin release.

Kyotorphin (Tyr-Arg) and its stable analogue [D-Arg]kyotorphin were injected into the substantia nigra of rats. Intranigral [D-Arg]-kyotorphin resulted in consistent ipsilateral rotational behavior which was naloxone-reversible. In comparison, intranigral Met-enkephalin induces naloxone-sensitive contralateral rotation. These results indicate a pharmacological effect of [D-Arg]kyotorphin in the substantia nigra that would appear to be independent of Met-enkephalin release.

Animals↗
PubMed1984

Physical dependence produced by chronic intracerebroventricular infusion of [D-Arg]kyotorphin or thiorphan to rats.

Two compounds, [D-Arg]kyotorphin and thiorphan, unique in their mechanisms for producing an opioid-like analgesic response, were infused for six days into the lateral cerebral ventricle of rats. [D-Arg]kyotorphin (62.5 micrograms/microliter per h) and thiorphan (75 micrograms/5 microliter per h), but not vehicle infused animals, displayed certain behaviors characteristic of precipitated morphine withdrawal upon naloxone (10 mg/kg i.p.) challenge. Acute intracerebroventricular (i.c.v.) administration of [D-Arg]kyotorphin (62.5 micrograms/5 microliter) or thiorphan (75 micrograms/5 microliter) and subsequent challenge with naloxone resulted in no abnormal behavior. These data indicate that compounds which produce their analgesic effect through the modulation of endogenous opioids can cause physical dependence.

Amino Acids, Sulfur↗