Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Piriform Cortex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1993

Topography and characteristics of specific binding sites for non-opioid gamma-type endorphins in the rat brain as studied by autoradiography with [35S]Met-desenkephalin-gamma-endorphin.

An in vitro autoradiographic study was performed to characterize specific rat brain binding sites for non-opioid neuroleptic-like gamma-type endorphins, using [35S]Met-des-enkephalin-gamma-endorphin ([35S]Met-DE gamma E; [35]S-beta-endorphins(5-17)) with high specific activity as radioligand. The binding sites appeared to be confined to rat forebrain regions, e.g., orbital cortex, frontal cortex, cingulate cortex, piriform cortex, nucleus accumbens, amygdala, mediodorsal nucleus of the thalamus and arcuate and periventricular nuclei of the hypothalamus. These regions are part of the mesocorticolimbic feedback circuit. Densitometric analysis of the autoradiographs revealed that the density of the binding sites was highest in the mediodorsal nucleus of the thalamus and the amygdala. Concentration-dependent displacement of [35S]Met-DE gamma E (500 pM) with DE gamma E yielded an IC50 of 0.6 nM whereas DE alpha E (beta-endorphin(6-16)) had an IC50 of 210 nM. Various endorphins, sharing the gamma-endorphin C terminus, displaced [35S]Met-DE gamma E to the same extent as non-labelled DE gamma E (at 10(-6) M) whereas non-endorphin peptides did not show displacing capacity. Possible relationships of the binding sites with opioid receptors were investigated. DAMGO (mu) and DPDPE (delta) displaced [35S]Met-DE gamma E to some extent at 10(-6) M whereas U69,593 (kappa) was inactive, suggesting that the binding sites for gamma-type endorphins may resemble mu- and delta-opioid receptors in some aspects. Similarly, relationships with dopamine receptors were investigated. Haloperidol partially displaced [35S]Met-DE gamma E whereas sulpiride, SKF38,393 and 3-PPP at 10(-6) M did not induce significant displacement. Thus, binding sites are distinct from dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1995

Changes in the cerebrocortical capillary network following venous sinus occlusion in cats.

BACKGROUND: Although the important protective effect of venous collateral pathways in sinus occlusion on parenchymal injury has been demonstrated in previous works, the vascular response in the capillary microcirculation itself after cerebral venous occlusion has not been fully elucidated. We examined the morphology of the capillary network after venous occlusion by relating stereologic morphometric parameters to changes in local cerebral blood flow and the development of brain edema. METHODS: Experimental venous sinus occlusion was induced by injection of 0.5 mL of cyanoacrylate into the superior sagittal sinus and by immediate ligation of both external jugular veins in chloralose-urethane anesthetized cats (n = 24). Capillaries in the adjacent cortex (marginal and suprasylvian cortex) and remote cortex (piriform cortex) were injected with Evans blue dye 2 minutes before sacrifice at 15-minute and 120-minute postsinus occlusion. The stereologic morphometric parameters including volume density, minimum intercapillary distance, capillary diameter, and number of perfused capillaries were computed on a fluorescence microscopic photograph using an image analysis system. Cerebral blood flow (CBF) was measured by hydrogen clearance method, and brain tissue water content was measured using the dry-wet method. RESULTS: In the cortex adjacent to the superior sagittal sinus, the volume density and the number of perfused capillaries were increased significantly (p < 0.02, and p < 0.05, respectively) and the minimum intercapillary distance was decreased significantly (p < 0.02) at 15 minutes after venous occlusion (n = 10). Cerebral blood flow (CBF) was also decreased to 53% of that in the control group (p < 0.01). Although the morphologic parameters returned to the control level by 120 minutes after venous occlusion, the CBF remained decreased after venous occlusion. No change was observed in the water content of the adjacent gray matter at 15 minutes after venous occlusion; however, it was increased (p < 0.05) at 120 minutes. CONCLUSION: These results indicate that the recruitment of reserve capillaries occurs during the early phase of venous occlusion. While CBF decreased to half of the control after venous occlusion, capillary perfusion remained above or near the control level until 120 minutes postocclusion, suggesting that venous recruitment would be potentially beneficial in clinical patients in the early stage of venous occlusion.

Animals↗
PubMed1992

Hypoxia-ischemia induces transforming growth factor beta 1 mRNA in the infant rat brain.

Transforming growth factor beta 1 (TGF beta 1) mRNA expression was examined after hypoxia-ischemia in rat brains using in situ hybridization. Twenty-one-day-old Wistar rats had unilateral ligation of the right carotid artery followed by either 15 or 90 min inhalational hypoxia. Fifteen min of hypoxia resulted in moderate damage with selective neuronal loss in cortical layer 3 and in the hippocampus of the ligated hemisphere. Seventy-two hours after hypoxia TGF beta 1 expression was markedly increased above control levels in those sites. Levels were normal after 120 h. Ninety min of hypoxia led to an infarction of the lateral cerebral cortex and hippocampus of the ligated hemisphere. One hour after hypoxia TGF beta 1 mRNA was expressed in the hippocampus of the damaged side. Seventy-two and 120 h after hypoxia, expressing cells were found throughout the cerebral cortex, piriform cortex, striatum, thalamus and hippocampus of the infarcted side. These data show that TGF beta 1 mRNA expression is induced after a hypoxic-ischemic insult in the brain. TGF beta 1 may be involved in post-asphyxial repair mechanisms.

Animals↗
PubMed1992

Distribution and cellular localization of preproenkephalin mRNA in the ovine brain and pituitary.

In this study in situ hybridization histochemistry was used to determine the regional and cellular localization of preproenkephalin (PPE) mRNA in the sheep brain and pituitary. Coronal brain sections were hybridized with an 35S-labelled synthetic 45-mer deoxyribonucleotide probe complementary to a portion of the bovine PPE gene. The specificity of the probe was confirmed by Northern blot analysis. The highest density of labelled cell bodies was found in the nucleus accumbens, caudate-putamen, olfactory tubercle, the central nucleus of the amygdala, the paraventricular nucleus of the hypothalamus, the suprachiasmatic nucleus and in the gigantocellular division of the medullary reticular formation. Labelled cells were also found in the olfactory bulb, prefrontal cortex, piriform cortex and cerebral cortex and in the vicinity of the locus coeruleus, parabrachial nucleus and the nucleus of the solitary tract. In the pituitary a dense PPE mRNA signal was observed in the intermediate lobe; cells in the anterior or neural lobe did not express PPE mRNA. The widespread distribution of cells containing PPE mRNA transcripts within the ovine brain agrees with a similar distribution in the rat. The data suggest that PPE neurons may be involved in diverse physiological functions including the processing of sensory and nociceptive information and in the regulation of endocrine and motor responses.

Animals↗
PubMed1992

Accumulation of calcitonin-gene related peptide-like immunoreactivity after hypoxic-ischaemic brain injury in the infant rat.

Unilateral carotid ligation in immature rats, followed by either 15 min (moderate group) or 90 min (severe group) of hypoxia were used to assess the effects of hypoxia-ischaemia (HI) on the accumulation of the neuropeptide calcitonin-gene related peptide (CGRP). Severe, but not moderate, HI produced a massive time-dependent increase in CGRP-like immunoreactivity throughout the damaged regions of the brain (neocortex, caudate-putamen, hippocampus) beginning at 24 h and maximal at 3-5 days after HI. By 11 days after HI levels appeared to have returned to baseline. The increased immunoreactivity was largely localized to presumed axon terminals contacting neurons, blood vessels and non-nerve cells. Scattered neurons in the cingulate cortex, piriform cortex and striatum also showed increased immunoreactivity in their soma. These results raise the possibility that CGRP may be involved in neuronal repair after HI in the infant brain.

Animals↗
PubMed1994

Production of specific antibodies against GABA transporter subtypes (GAT1, GAT2, GAT3) and their application to immunocytochemistry.

Polyclonal subtype-specific antibodies were developed against three subtypes of GABA transporters (GAT1, GAT2 and GAT3). By immunoblot analysis, each antibody detected a single band that could be blocked by absorption of the antibody with the respective antigen. GAT2 was found in various tissues, while GAT1 and GAT3 were detected only in the brain. GAT1 was distributed throughout the brain with the highest amount in the olfactory bulb, CA3 region of the hippocampus, layer I of the cerebral cortex, piriform cortex, superior colliculus, interpeduncular nucleus and nucleus spinal tract of the trigeminal nerve, while the GAT3 was densely found in the olfactory bulb, thalamus, hypothalamus, pons and medulla, globus pallidus, central gray, substantia nigra, deep cerebellar nuclei and nucleus spinal tract of the trigeminal nerve but not in the hippocampus, cerebral cortex, caudate-putamen and cerebellar cortex. GAT2 immunoreactivity was faint throughout the brain but was concentrated in the arachnoid and ependymal cells. Both GAT1 and GAT3 were found in the neuropil but not in the cell bodies nor in the white matter. These results suggest that GAT1, GAT2 and GAT3 are expressed in different cells and that GAT1 and GAT3 are involved in distinct GABAergic transmission while GAT2 may be related to non-neuronal function.

Amino Acid Sequence↗
PubMed1994

Distribution of messenger RNA for the vasopressin V1a receptor in the CNS of male and female rats.

The distribution of cells expressing mRNA encoding a vasopressin V1a receptor (V1aR) was examined in Long-Evans male and female rats by in situ hybridization using a [35S]cRNA probe. Specific hybridization to the vasopressin V1aR mRNA was evident in cells of the frontal cortex, piriform cortex, internal granular layer and the medial, dorsal, ventral and lateral portion of the anterior olfactory nucleus, zona limitans of the islands of Calleja, suprachiasmatic nucleus, CA1, CA2, CA3 and dentate gyrus of the hippocampus, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus, lateral habenular nucleus, and the molecular and granular cell layers of the cerebellum. The cerebellum, olfactory nucleus and the dentate gyrus appeared to be the most intensely labeled areas, while all other areas exhibited a lower level of expression. The anatomical distribution and the amount (as measured by optical density) of V1aR mRNA labeling was identical between male and female rats. This indicates that unlike the vasopressin gene itself, the expression of the vasopressin V1aR mRNA does not exhibit sexual dimorphism. These data demonstrate a wide spread distribution in the expression of the vasopressin V1aR mRNA in the CNS of male and female rats. This information on the anatomical distribution of the V1aR mRNA when combined with data concerning the anatomical distribution of the V1a binding sites, provides new information on the possible pre- and post-synaptic location of these neuropeptide receptors.

Animals↗
PubMed1996

Expression of the 27,000 mol. wt heat shock protein following kainic acid-induced status epilepticus in the rat.

Western analysis and immunohistochemistry were used to determine the time-course and the distribution of the 27,000 mol. wt heat shock protein, Hsp27, in rat brain following systemic administration of kainic acid. No Hsp27 immunoreactivity was detected in naive control animals or in rats that failed to develop status epilepticus. Hsp27 immunoreactivity was detected as early as 12 h in the parietal cortex, piriform cortex and the hippocampus of rats that developed status epilepticus. The number of cells expressing Hsp27 and the intensity of Hsp27 immunoreactivity were increased 24 h after kainic acid administration. Hsp27 immunoreactivity was still observed seven days post-kainic acid injection. The morphology of the Hsp27-positive cells and double immunofluorescence against Hsp27 and glial fibrillary acidic protein revealed that Hsp27-positive cells were astrocytes. In addition, the distribution of Hsp27 suggested that astrocytic Hsp27 was dependent on excitation-induced metabolic stress rather than the direct effect of kainic acid on astrocytes.

Animals↗
PubMed1990

Effect of haloperidol on immunoreactive neuropeptide Y in rat cerebral cortex and basal ganglia.

To clarify the dopaminergic regulation of neuropeptide Y (NPY) neurons, the effect of haloperidol on NPY in basal ganglia and the cerebral cortex of the rat brain was investigated by sensitive radioimmunoassay and immunocytochemistry using antiserum against rat NPY. After repeated intraperitoneal injections of haloperidol (5 mg/kg) for 6 days, the content of immunoreactive NPY was significantly decreased in the caudate-putamen, but significantly increased in the lateral prefrontal cortex. After treatment for 21 days, the content of immunoreactive NPY in the caudate-putamen remained significantly low, but the extent of change in the lateral prefrontal cortex diminished. In the medial prefrontal cortex, piriform cortex, parietal cortex and nucleus accumbens, no significant changes were found after treatment for either 6 or 21 days. These findings were compatible with those obtained by immunocytochemistry using the same antiserum: an increase of immunoreactive fibers and terminals in the lateral prefrontal cortex and their decrease in the caudate-putamen. However, in the nucleus accumbens the density of immunoreactive fibers and terminals was decreased in the rostral portion, but not in the caudal portion after haloperidol treatment for 6 and 21 days. These findings suggest that dopaminergic afferents region-specifically regulate dopamine-sensitive NPY neurons in the rat brain.

Animals↗
PubMed2006

Central alpha1-adrenergic system in behavioral activity and depression.

Central alpha(1)-adrenoceptors are activated by norepinephrine (NE), epinephrine (EPI) and possibly dopamine (DA), and function in two fundamental and opposed types of behavior: (1) positively motivated exploratory and approach activities, and (2) stress reactions and behavioral inhibition. Brain microinjection studies have revealed that the positive-linked receptors are located in eight to nine brain regions spanning the neuraxis including the secondary motor cortex, piriform cortex, nucleus accumbens, preoptic area, lateral hypothalamic area, vermis cerebellum, locus coeruleus, dorsal raphe and possibly the C1 nucleus of the ventrolateral medulla, whereas the stress-linked receptors are present in at least three areas including the paraventricular nucleus of the hypothalamus, central nucleus of the amygdala and bed nucleus of the stria terminalis. Recent studies utilizing c-fos expression and mitogen-activated protein kinase activation have shown that various diverse models of depression in mice produce decreases in positive region-neural activity elicited by motivating stimuli along with increases in neural activity of stress areas. Both types of change are attenuated by various antidepressant agents. This has suggested that the balance of the two networks determines whether an animal displays depressive behavior. A central unresolved question concerns how the alpha(1)-receptors in the positive-activity and stress systems are differentially activated during the appropriate behavioral conditions and to what extent this is related to differences in endogenous ligands or receptor subtype distributions.

Animals↗
PubMed2005

CAT 53: a protein phosphatase 1 nuclear targeting subunit encoded in the MHC Class I region strongly expressed in regions of the brain involved in memory, learning, and Alzheimer's disease.

We identified CAT 53 by cDNA hybridization selection as an expressed sequence tag (EST), located in the vicinity of HLA-C and designated as CAT (for HLA-C associated transcript) 53. CAT 53 encodes a protein described by others and commonly known as phosphatase 1 nuclear targeting subunit (PNUTS). PNUTS is a potent inhibitor of nuclear serine/threonine protein phosphatase 1 (PP1). We present the genomic organization of CAT 53, localize specific sites of mRNA transcription in thin sections of mouse brain by in-situ hybridization, and perform a structural analysis of the peptide domains. We also characterize the protein expression pattern for PNUTS by Western blotting and immunohistochemistry with PNUTS antibody in Alzheimer's disease (AD) brains and age-matched control brains. In-situ hybridization and immunohistochemistry analysis of human and mouse brain show high CAT 53 expression in the olfactory cortex, piriform cortex, and hippocampus. Very high expression of CAT 53 was found mainly in the hippocampus, frontal, and entorhinal cortex of control brains and in the neurofibrillary tangles of AD brain. In the hippocampus, CAT 53 is expressed in CA1 and CA3 cell layers and in the dentate gyrus. The hippocampus is known to play a fundamental role in learning and episodic memories and has been implicated in a number of neurological and psychiatric disorders, including AD, epilepsy, and schizophrenia. Our findings suggest that PNUTS, encoded by CAT 53 on 6p21.3, may have a role in the progression of AD.

Aged↗
PubMed2004

Selective changes in gene expression in cortical regions sensitive to amphetamine during the neurodegenerative process.

Gene expression profiles in several brain regions of adult male rats were evaluated following a d-amphetamine (AMPH) exposure paradigm previously established to produce AMPH neurotoxicity. Escalating doses of AMPH (5-30 mg/kg) were given over the course of 16 h per day in an 18 degrees C environment for 2 days. This paradigm produces neurotoxicity but eliminates or minimizes the hyperthermia and seizure activity that might influence gene expression in a manner unrelated to the neurotoxic effects of AMPH. The expression of 1185 genes was monitored in the striatum, parietal cortex, piriform cortex and posteriolateral cortical amygdaloid nucleus (PLCo) using cDNA array technology, and potentially significant changes were verified by RT-PCR. Gene expression was determined at time points after AMPH when neurodegeneration was beginning to appear (16 h) or maximal (64 h). Expression was also determined 14 days after AMPH to find long-term changes in gene expression that might be biomarkers of a neurotoxic event. In the parietal cortex there was a two-fold increase in neuropeptide Y precursor protein mRNA whereas nerve growth factor-induced receptor protein I-A and I-B mRNA decreased 50% at 16 h after the end of AMPH exposure. Although these changes in expression were not observed in the PLCo, insulin-like growth factor binding protein 1 mRNA was increased two-fold in the PLCo at 16 and 64 h after AMPH. Changes in gene expression in the cortical regions were all between 1.2- and 1.5-fold 14 days after AMPH but some of these changes, such as annexin V increases, may be relevant to neurotoxicity. Gene expression was not affected by more than 1.5-fold at the time points in the striatum, although 65% dopamine depletions occurred, but the plasma membrane-associated dopamine transporter and dopamine D2 receptor were decreased about 40% in the substantia nigra at 64 h and 14 days post-AMPH. Thus, the 2-day AMPH treatment produced a few changes in gene expression in the two-fold range at time points 16 h or more after exposure but the majority of expression changes were less than 1.5-fold of control. Nonetheless, some of these lesser fold-changes appeared to be relevant to the neurotoxic process.

Amphetamine↗
PubMed2000

Effect of thyroid hormone deficiency on developmental expression of goalpha gene in the brain of neonatal rats by competitive RT-PCR and in situ hybridization histochemistry.

Goalpha is a guanine nucloetide-binding regulatory protein alpha subunit which is mainly distributed in the central nervous system, but it has not previously been reported how it is regulated by thyroid hormone in the brain of neonatal rat at transcriptional levels. In this report, we used quantitative competitive reverse transcriptional PCR to quantify the effects of TH deficiency on Goalpha gene expression in the brain of neonatal rat at mRNA levels. It was found that Goalpha mRNA levels in the brain of 14-day-old rats significantly increased over 3-fold after induction of perinatal hypothyroidism, and declined markedly after treatment of thyroxine replacement. In situ hybridization histochemistry was further employed to observe the time-course and spatial expression of Goalpha gene in the brain of neonatal rats affected by thyroid hormone deficiency during the developmental period. The data showed that perinatal hypothyroidism can enhance Goalpha mRNA levels in the temporal cortex, sensorimotor cortex, piriform cortex, amygdala, hippocampal CA1-4 subfields, dentate gyrus, arcuate nucleus (AR) and ventromedial hypothalamic nucleus (VMH) of hypothalamus, but not in the striate cortex, cingulate cortex, claustrum, caudate/putamen and thalamus in the brain of rat at 7-21 days post-partum. The results suggest that up-regulation of Goalpha gene expression may be one kind of common mechanism responsible for neurological deficits in some brain areas arising from thyroid hormone deficiency in the critical periods of neonatal rats.

Animals↗
PubMed2001

Kainic acid-induced substantia nigra seizure in rats: behavior, EEG and metabolism.

RATIONALE: In order to clarify the role of substantia nigra pars reticulata (SNr) upon the development of epileptic seizure, kainic acid (KA) was injected into a unilateral SNr. MATERIALS AND METHODS: Wistar rats weighing 250-350 g were used. A stainless-steel cannula and depth electrode were inserted stereotaxically into the left substantia nigra pars reticulata (SNr). At 7 days after surgery, 1.0 microg of KA was injected into the left SNr. Experiment 1: In eight rats, behavior and electroencephalograms (EEG) were continuously recorded for about 30 h, and intermittently monitored following 1 month. Experiment 2: Two hours after KA injection into SNr, rats demonstrated status epilepticus. Then, 100 microCi/kg of [(14)C]2-deoxyglucose (2-DG) was intravenously injected in seven rats, and the rats were processed for autoradiographic study. RESULTS: Changes in behavior and EEG: On EEG, a secondary generalized seizure status was observed at about 70 min after KA injection. In video, limbic seizure manifestations such as salivation were observed as a initial symptom and followed by rolling and generalized tonic seizures. [(14)C]deoxyglucose autoradiographic study demonstrated increased local cerebral glucose metabolism in the medial and lateral septal nucleus, substantia nigra, hippocampus, parietal cortex, piriform cortex, medial and lateral geniculate nucleus, anterodorsal, lateral and ventral nucleus of the thalamus, amygdala and midbrain reticular formation. SUMMARY: The result suggested that the substantia nigra played an important role in the secondary generalization in the substantia nigra seizure model due to the decreased function of the GABAergic projection system induced by an excessive epileptic excitation of SNr.

Action Potentials↗
PubMed2002

Electrophysiological, behavioral and metabolical features of globus pallidus seizures induced by a microinjection of kainic acid in rats.

There has been few studies of the globus pallidus in relation to epilepsy. In this study, kainic acid (KA)-induced globus pallidus seizure was electrophysiologically, electroencephalographically, histopathologically and metabolically investigated in rats. Sixteen Wistar rats weighing 250-350 g were used. Under intraperitoneal pentobarbital anesthesia, a stainless-steel cannula was inserted stereotaxically into the left globus pallidus pars externa (GPe) for KA injection. For recording EEG, a depth electrode was inserted into the left GPe, just posterior to the tip of the injection guide cannula. Electrodes were also inserted into the right globus pallidus and bilateral sensorimotor cortex (SMC). EEG changes after KA injection were classified as follows: Continuous low-voltage spikes were observed in the left GPe on EEG at stage 1. Intermittent multiple spikes and wave complexes began to propagate to the left SMC at stage 2. Continuous spikes and wave complexes began to propagate to the bilateral SMC at stage 3. Secondary generalized seizures were observed at stage 4. Globus pallidus seizures recurred every 7-9 min and lasted for 4-6 h. However, the seizures gradually subsided and became normal within 18 h. No spontaneous seizure was detected for the next 30 days. Histopathological study revealed a small gliotic lesion with neuronal cell loss around the cannula tip. Neither degeneration nor neuronal cell loss in the ipsilateral hippocampus were observed. The autoradiogram using [14C]2-deoxyglucose during seizure status demonstrated a remarkable increase of local cerebral glucose utilization not only in the GPe but also in the GPi. An increase glucose metabolism was also found in the follows: the medial and lateral septal nucleus, substantia nigra, hippocampus, frontal cortex, parietal cortex, piriform cortex, entorhinal cortex, accumbens nucleus, ventral and lateral nucleus of the thalamus, amygdala, and ventral nucleus of hypothalamus. KA injection into the unilateral GPe evoked not only epileptic excitation of the cortex but also transient enhancement of the globus pallidus-substantia nigra circuit.

Action Potentials↗
PubMed2002

The medial prefrontal cortex mediates 3-methoxytyramine-induced behavioural changes in rat.

L-3,4-Dihydroxyphenylalanine (L-DOPA) remains a common treatment for Parkinson's disease; however, side effects (i.e., dyskinesia and hallucinations) also remain problematic. We recently reported that the dopamine metabolite 3-methoxytyramine causes stereotypy in rats via dopamine receptors, raising the possibility that 3-methoxytyramine is involved in the adverse side effects of chronic L-DOPA treatment. Thus, the present study examined the sites of 3-methoxytyramine action in the rat brain. After intracerebroventricular administration of 3-methoxytyramine, significantly more neurones expressed c-Fos in mesocortico-limbic dopamine areas including frontal cortex, medial prefrontal cortex, parietal cortex, piriform cortex, the nucleus accumbens shell, and ventral tegmental area. 3-Methoxytyramine injection into the medial prefrontal cortex specifically resulted in behavioural changes characteristic of those elicited by the more general intracerebroventricular injection of 3-methoxytyramine. This suggests that the medial prefrontal cortex mediates the 3-methoxytyramine-induced behavioural changes and that a reduction of its action there may alleviate the adverse effects of chronic L-DOPA treatment.

Animals↗
PubMed2002

Lu 28-179 labels a sigma(2)-site in rat and human brain.

1'-[4-[1-(4-Fluorophenyl)-1H-indol-3-yl]-1-butyl]spiro[isobenzofuran-1(3H),4'-piperidine] (Lu 28-179) or Siramesine is a sigma-ligand with high specificity for sigma(2)-sites, has been tritiated to directly label these sites in brain. [(3)H]Lu 28-179 bound in a saturable manner to homogenates prepared from rat brain or human cortices with high affinity (K(d)=2.2 and 1.1 nM, respectively) and moderate capacity (B(max)=50+/-12 and 26+/-3 fmol mg tissue(-1), respectively). The rank order of affinity for [(3)H]Lu 28-179 binding to homogenates from human and rat brain was: Lu 28-179>ifenprodil=haloperidol>1,3-di(2-tolyl)-guanidine (DTG)>(-)pentazocinez.Gt;(+)pentazocine. Using in vitro receptor autoradiography to rat brain sections [(3)H]Lu 28-179 binding was shown to be most predominant in the cerebral cortex, piriform cortex, hippocampal formation (CA1-CA3 and dentate gyrus), superior colliculus, molecular layer of the cerebellar cortex and locus coeruleus. Overall, these data are consistent with [(3)H]Lu 28-179 labelling a sigma(2)-like binding site.

Aged↗
PubMed2000

Agonist-stimulated [35S]GTPgammaS binding in brain modulation by endogenous adenosine.

Coupling of receptors to G-proteins can be assessed by the ability of specific agonists to stimulate [35S]GTPgammaS binding in both brain membranes and sections in the presence of excess GDP. In some brain regions, however, high basal activity makes it difficult to detect agonist-stimulated [35S]GTPgammaS binding. The present study suggests a modification of the assay to reduce basal [35S]GTPgammaS binding and thus increase the signal:noise ratio. Adenosine A1 receptors belong to the class of G-protein-coupled receptors that activate Gi/Go proteins in brain. In the present study, the A1 agonist R(-)N6-(2-phenylisopropyl)adenosine (R-PIA) stimulated [35S]GTPgammaS binding in brain regions known to contain A1 receptors, including cerebellum, hippocampus and dentate gyrus, medial geniculate body, superior colliculus, certain thalamic nuclei, cerebral cortex, piriform cortex, caudate-putamen, and nucleus accumbens. Treatment of sections and membranes with adenosine deaminase (ADase), which is typically used in adenosine assays to eliminate endogenous adenosine, reduced basal [35S]GTPgammaS binding. In addition, for cannabinoid and mu-opioid agonists, the percent stimulation of [35S]GTPgammaS binding was approximately doubled when ADase was included in the assay. These results suggest that endogenous adenosine contributes significantly to basal [35S]GTPgammaS binding in certain brain regions, and that this activity may be reduced by the addition of ADase, thus improving the signal:noise ratio of agonist-stimulated [35S]GTPgammaS binding.

Adenosine↗