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Biomedical subjects

R Quirion

Publications and source records attributed to R Quirion.

At least 343 records · Page 19Linked to original sources
PubMed1986

Kappa opioid receptors in human lumbo-sacral spinal cord.

[3H]Etorphine and [3H]ethylketocyclazocine bind with high affinity (Kd between 0.25-2.0 nM) to a single class of sites in human lumbo-sacral spinal cord. Other ligands such as [3H]morphine, [3H]dihydromorphine and [3H]D-Ala2, D-Leu5-enkephalin (DADLE) did not bind to significant number of sites under our incubation conditions. Ligand selectivity pattern strongly suggests that [3H]etorphine labels kappa opioid binding sites in the human lumbo-sacral spinal cord since benzomorphans and oripavines are much more potent than mu and delta agonists. Furthermore, [3H]etorphine and [3H]ethylketocyclazocine binding is sensitive to high concentrations of DADLE suggesting that these sites are of the kappa 2 sub-type. Finally, the visualization of these sites by receptor autoradiography demonstrates that they are mainly concentrated in lamina II and III of the dorsal horn. Moderate densities of sites are present around the central canal. Thus, it is possible that kappa opioid binding sites could be involved in the control of sensory and autonomic functions in the human lumbo-sacral spinal cord.

Adult↗
PubMed1986

Transmitter-replacement therapy in Alzheimer's disease using intracerebroventricular infusions of receptor agonists.

Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action.

Alzheimer Disease↗
PubMed1986

Neurotransmitter and receptor deficits in senile dementia of the Alzheimer type.

Multiple neurotransmitter systems are affected in senile dementia of the Alzheimer's type (SDAT). Among them, acetylcholine has been most studied. It is now well accepted that the activity of the enzyme, choline acetyltransferase (ChAT) is much decreased in various brain regions including the frontal and temporal cortices, hippocampus and nucleus basalis of Meynert (nbm) in SDAT. Cortical M2-muscarinic and nicotinic cholinergic receptors are also decreased but only in a certain proportion (30-40%) of SDAT patients. For other systems, it appears that cortical serotonin (5-HT)-type 2 receptor binding sites are decreased in SDAT. This diminution in 5-HT2 receptors correlates well with the decreased levels of somatostatin-like immunoreactive materials found in the cortex of SDAT patients. Cortical somatostatin receptor binding sites are decreased in about one third of SDAT patients. Finally, neuropeptide Y and neuropeptide Y receptor binding sites are distributed in areas enriched in cholinergic cell bodies and nerve fiber terminals and it would be of interest to determine possible involvement of this peptide in SDAT. Thus, it appears that multi-drug clinical trials should be considered for the treatment of SDAT.

Alzheimer Disease↗
PubMed1986

Characterization and distribution of receptors for the atrial natriuretic peptides in mammalian brain.

Both rat 125I-labeled atrial natriuretic polypeptide [125I-ANP or atrial natriuretic factor fragment ANF-(99-126)] and human 125I-ANP [125I-alpha-ANP or human ANF-(99-126)] bind with high specificity and affinity (Kd = 20-80 pM) to an apparent single class of sites in guinea pig brain. The ligand selectivity pattern demonstrates that ANF-(101-126) greater than ANF-(99-126) greater than ANF-(103-125) greater than ANF-(103-123) on 125I-alpha-ANP binding sites. [International nomenclature starting at the end of the signal peptide of the recently sequenced prepropeptide is used; thus, ANF-(101-126) corresponds to the earlier designation ANF-(8-33), ANF-(103-123) to rat atriopeptin I, and ANF-(103-125) to rat atriopeptin II.] Similar results have been reported in peripheral tissues, which indicate that central and peripheral ANP binding sites have fairly similar structural requirements. In vitro receptor autoradiography shows that in the guinea pig brain, 125I-ANP binding sites are highly concentrated in the external plexiform layer of the olfactory bulb, subfornical organ, various thalamic nuclei, medial geniculate nucleus, and cerebellum. Lower densities are found in the central nucleus of the amygdala, dentate gyrus, hippocampus, and area postrema. Most remaining regions contain much lower densities of sites. In rat brain, 125I-ANP binding sites are differentially distributed, with high densities in the subfornical organ, area postrema, and linings of ventricles but low densities in the thalamus and cerebellum. In monkey brain, 125I-ANP binding sites are concentrated in the cerebellum. The presence of high densities of 125I-ANP binding sites in various brain regions strongly suggests the existence of a family of brain-heart peptides, in analogy to the well-known brain-gut peptides. Moreover, the extensive distribution of 125I-ANP binding sites in mammalian brain suggests that the possible roles of ANP/ANF-like peptides in brain are not restricted to the central regulation of cardiovascular parameters.

Animals↗
PubMed1986

Effect of imipramine on the circadian rhythm of plasma melatonin in unipolar depression.

The authors took a series of 20 serum samples over a 24-hr period for measurement of melatonin in four men and six women with Major Depressive Disorder (DSM-III), at baseline (depressed) and after 4 weeks on imipramine (150-200 mg/day) after achieving clinical remission. After successful treatment with imipramine, 24-hr secretion and peak levels of melatonin were significantly higher than at baseline, with no difference in time of peak level. Testing after 2 weeks of treatment (four subjects), with only a partial or no clinical response, revealed no differences compared with baseline. The therapeutic efficacy of imipramine may be associated with an enhancement of noradrenergic activity.

Adult↗
PubMed1986

Mu opioid receptor binding sites in human brain.

Our experiments focused on the examination of the distribution of mu opioid receptor binding sites in normal human brain using the highly selective ligand [3H]DAGO, in both membrane binding assay and in vitro receptor autoradiography. Mu opioid binding sites are very discretely distributed in human brain with high densities of sites found in the posterior amygdala, caudate, putamen, hypothalamus and certain cortical areas. Moreover the autoradiographic distribution of [3H]DAGO binding sites clearly reveals the discrete lamination (layers I and III-IV) of mu sites in cortical areas.

Autoradiography↗
PubMed1986

Ontogeny of substance P receptor binding sites in rat brain.

The ontogeny of substance P (SP) receptor binding sites in rat brain has been studied using both membrane binding assays and in vitro receptor autoradiography. The density of SP binding sites is maximal 1 d before birth and decreases thereafter to reach adult values 14 d after birth. During the early postnatal period, the distribution of SP binding sites undergoes major modifications. For example, very high densities of SP binding sites are present in most brain stem nuclei from 1 to 14 d after birth, while it is not the case in adults. In the striatum, SP receptors are distributed in a "patchy" manner early after birth, while it is much more homogeneous in the adult. This demonstrates that SP receptors undergo major redistributions during postnatal development. The very high density of SP binding sites present in the brain at its early stages of development may indicate that SP could be an important factor involved in the early organization of the CNS.

Animals↗
PubMed1985

Platelet 3H-imipramine binding distinguishes depression from Alzheimer dementia.

Platelet 3H-imipramine binding and serotonin uptake were studied simultaneously in normal subjects and in depressed, parkinsonian and Alzheimer's disease patients to investigate the usefulness of these variables in the diagnosis of depression in the elderly. Whereas Vmax of platelet serotonin uptake was significantly reduced in all patient groups compared to age matched normal subjects, the density of 3H-imipramine binding was reduced in depressed patients only. The lower Bmax values in depressed patients was independent of patient age. These data suggest that platelet 3H-imipramine binding may be a useful laboratory index which discriminates depression from dementia in the elderly.

Age Factors↗
PubMed1985

Localization and characterization of brain somatostatin receptors as studied with somatostatin-14 and somatostatin-28 receptor radioautography.

The localization and characterization of receptors for somatostatin-14 (S-14) and somatostatin-28 (S-28) were studied in the rat brain using the iodinated agonists [Tyr0,D-Trp8]S-14 and [Leu8,D-Trp22,Tyr25]S-28 as tracers. Slide-mounted frozen sections were used for the radioautographic localization and biochemical characterization of somatostatin receptors. In the latter case counting was performed on scraped off serial sections from rostral regions of the brain. Specificity studies demonstrated that either tracer could be displaced with S-28, S-14 or their agonists. The N-terminus fragment (1-12) of S-28 as well as a number of unrelated peptides were unable to compete with either tracer, indicating that the binding capacity for ligand-receptor recognition is located in the C-terminal portion of S-28. Scatchard analysis of saturation curves gave a one-site interaction with Kd values of 0.42 +/- 0.09 nM and 0.32 +/- 0.04 nM for the S-14 and S-28 iodinated agonists, respectively. By radioautography, the distribution of receptors for both S-14 and S-28 appeared very similar with high levels of binding in the deep layers of the cortex, the cingulate cortex, the claustrum, the locus coeruleus and most structures of the limbic system. Treatment with cysteamine, which caused a somatostatin depletion in the brain, was required to observe labeling in the hypothalamus. In some caudal areas of the brain, especially in the cerebellar nuclei, the solitary tract nucleus and the nucleus of the vagus nerve, only labeling with the S-28 agonist could be detected. This S-28 binding could be displaced by native S-14 (10(-6) M). Generally, there was a correlation between the localization of somatostatin receptors and that of immunoreactive somatostatin, as evaluated by immunocytochemistry. However, in some areas, an inverse correlation between receptor and peptide concentrations was observed. These results are in agreement with previous data suggesting that somatostatin could act as a neurotransmitter or neuromodulator in several brain areas.

Animals↗
PubMed1985

Characterization of binding sites for two classes of calcium channel antagonists in human forebrain.

1,4-Dihydropyridine ([3H]PN200-110) and phenylalkylamine ([3H](-)D-888) bound with high affinity to human brain cortex homogenates. The ligand selectivity pattern indicates that [3H]PN200-110 binding was inhibited by related 1,4-dihydropyridine analogues but not by phenylalkylamines. On the other hand, phenylalkylamines were potent inhibitors of [3H](-)D-888 binding in human brain. The radioautographic distribution of [3H]PN200-110 and [3H](-)D-888 binding sites demonstrates that 1,4-dihydropyridine and phenylalkylamine sites were similarly distributed in human forebrain.

Aniline Compounds↗
PubMed1985

Phencyclidine binding sites in the nucleus accumbens and phencyclidine-induced hyperactivity are decreased following lesions of the mesolimbic dopamine system.

[3H]Phencyclidine [( 3H]PCP) binding to rat nucleus accumbens, hippocampal and striatal membranes, and PCP-induced locomotor hyperactivity were assessed following selective lesions of the mesolimbic dopaminergic system. 6-Hydroxydopamine (6-OHDA) injections into the A10 region of the ventral tegmental area or into the accumbens itself resulted in a blockade of PCP's stimulatory effects and a highly significant reduction in the number of [3H]PCP binding sites and dopamine content of the nucleus accumbens. However, destruction of the dopaminergic mesolimbic fibers did not significantly alter hippocampal or striatal [3H]PCP binding. The data suggest that PCP elicits its locomotor stimulating effects via an interaction with PCP binding sites located mostly on mesolimbic dopaminergic terminals within the nucleus accumbens.

Animals↗
PubMed1985

Evidence for the existence of serotonin type-2 receptors on cholinergic terminals in rat cortex.

Levels of serotonin type-2 receptors and choline acetyltransferase (ChAT) were measured in various rat brain regions following unilateral lesions of the nucleus basalis magnocellularis (nBM). As expected, lesions of the nBM markedly decrease cortical ChAT activity. Moreover, [3H]ketanserin (serotonin type-2) binding is significantly decreased in lamina IV of the anterior and middle cortex on the lesioned vs control side. [3H]ketanserin binding in the striatum is not affected by lesions of the nBM. Autoradiograms of [3H]ketanserin binding in lesioned animals show similar results. This suggests that at least a certain proportion of serotonin type-2 receptor binding sites are located on cholinergic terminals in lamina IV of the rat cortex. Therefore, further investigations on cholinergic-serotonergic interactions in the cortex and their possible involvement in senile dementia of the Alzheimer's type appear to be highly relevant.

Alzheimer Disease↗
PubMed1985

Autoradiographic distribution of [3H]dexoxadrol (a phencyclidine-related ligand) binding sites in rat and human brain.

[3H]dexoxadrol, a dissociative anesthetic, binds with high affinity to specific sites in rat brain (membrane binding and light microscopic autoradiography). Various phencyclidine (PCP) analogues compete for [3H]dexoxadrol sites in a slightly different manner than against [3H]PCP binding sites. As for [3H]PCP binding, [3H]dexoxadrol binding sites are highly concentrated in brain regions such as the cortex and the hippocampus. However, other areas such as the hypothalamus are enriched only in [3H]dexoxadrol binding sites. This suggests that [3H]dexoxadrol binds to PCP-related sites in certain brain regions but not in others. In the human forebrain, [3H]dexoxadrol binding sites are distributed as in the rat brain and mainly found in the caudate, putamen and cortex.

Animals↗
PubMed1985

Biochemical characterization and autoradiographic localization of central substance P receptors using [125I]physalaemin.

The binding of [125I]physalaemin to rat brain slices was investigated. Radiolabeled physalaemin bound with high affinity (Kd = 0.3 nM) to a single class of sites (Bmax = 22 fmol/mg protein). Kinetic studies indicated that binding was time-dependent and all specific binding was reversible. Pharmacology studies indicated that specific [125I]physalaemin binding was inhibited by structurally related peptides such as substance P and eledoisin. Biochemical studies indicated that specific binding of radiolabeled physalaemin was greatly reduced if the brain slices were pretreated with heat, trypsin or N-ethyl maleimide. Autoradiographic studies indicated that the [125I]physalaemin binding sites were discretely distributed throughout the brain. Highest grain densities were present in the olfactory bulb, dentate gyrus, amygdala, superficial layers of the superior colliculus, subiculum, dorsal parabrachial nucleus, locus coeruleus, nucleus tractus solitarii and dorsal horn of the spinal cord. Moderate grain densities were present in the nucleus accumbens, olfactory tubercle, pyriform cortex, striatum, hippocampus, inferior colliculus and central gray of the midbrain. Low grain densities were present in most thalamic nuclei, the substantia nigra and cerebellum. The corpus callosum and controls treated with 1 microM unlabeled physalaemin had negligible levels of binding. The unique pharmacological and regional distribution data obtained suggest that [125I]physalaemin may serve as a valuable probe to study central substance P receptors.

Animals↗