Biomedical subjects

A Morel

Publications and source records attributed to A Morel.

At least 19 recordsLinked to original sources

PubMed1995

Topography of visual cortex connections with frontal eye field in macaque: convergence and segregation of processing streams.

The primate visual system consists of at least two processing streams, one passing ventrally into temporal cortex that is responsible for object vision, and the other running dorsally into parietal cortex that is responsible for spatial vision. How information from these two streams is combined for perception and action is not understood. Visually guided eye movements require information about both feature identity and location, so we investigated the topographic organization of visual cortex connections with frontal eye field (FEF), the final stage of cortical processing for saccadic eye movements. Multiple anatomical tracers were placed either in parietal and temporal cortex or in different parts of FEF in individual macaque monkeys. Convergence from the dorsal and ventral processing streams occurred in lateral FEF but not in medial FEF. Certain extrastriate areas with retinotopic visual field organizations projected topographically onto FEF. The dorsal bank of the superior temporal sulcus projected to medial FEF; the ventral bank, to lateral FEF, and the fundus, throughout FEF. Thus, lateral FEF, which is responsible for generating short saccades, receives visual afferents from the foveal representation in retinotopically organized areas, from areas that represent central vision in inferotemporal cortex and from other areas having no retinotopic order. In contrast, medial FEF, which is responsible for generating longer saccades, is innervated by the peripheral representation of retinotopically organized areas, from areas that emphasize peripheral vision or are multimodal and from other areas that have no retinotopic order or are auditory.

Animals↗

PubMed1992

Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus.

The antidiuretic effect of arginine vasopressin (AVP) is mediated by renal-type (V2) receptors linked to adenylyl cyclase. We report here the cloning of the rat kidney V2 AVP receptor complementary DNA that encodes a 370-amino-acid protein with a transmembrane topography characteristic of G protein-coupled receptors, and with similarity to the V1a (hepatic) AVP receptor in its seven membrane-spanning domains. Expression of the cloned cDNA in mammalian cells showed specific ligand binding and activity characteristic of the native V2 AVP receptor. The receptor messenger RNA is detected only in the kidney. The human V2 receptor gene has been localized to the long arm of the X chromosome close to the locus for nephrogenic diabetes insipidus, an X-linked recessive disorder characterized by renal resistance to the antidiuretic action of AVP.

Adenylyl Cyclases↗

PubMed1992

Molecular cloning and expression of a rat V1a arginine vasopressin receptor.

The neurohypophyseal hormone arginine vasopressin has diverse actions, including the inhibition of diuresis, contraction of smooth muscle, stimulation of liver glycogenolysis and modulation of adrenocorticotropic hormone release from the pituitary. Arginine vasopressin receptors are G protein-coupled and have been divided into at least three types; the V1a (vascular/hepatic) and V1b (anterior pituitary) receptors which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+, and the V2 (kidney) receptor which is coupled to adenylate cyclase. We report here the cloning of a complementary DNA encoding the hepatic V1a arginine vasopressin receptor. The liver cDNA encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The messenger RNA corresponding to the cDNA is distributed in rat tissues known to contain V1a receptors.

Amino Acid Sequence↗

PubMed1992

Subdivisions and connections of auditory cortex in owl monkeys.

The organization and connections of auditory cortex in owl monkeys, Aotus trivirgatus, were investigated by combining microelectrode mapping methods with studies of architecture and connections in the same animals. In most experiments, portions of auditory cortex were first explored with microelectrodes, neurons were characterized as responsive or not to auditory stimuli, and best frequencies were determined whenever possible. Most recordings were in cortex previously designated as primary (A-I) and rostral (R) auditory fields (Imig et al. J Comp Neurol 171:111, '77) and in a newly defined rostrotemporal field (RT) located rostral to R. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and fluorescent tracers were placed in electrophysiologically identified locations of A-I, R, and RT; the posterolateral (PL) and anterolateral (AL) divisions of a narrow belt of auditory cortex lateral and adjacent to A-I and R; cortex of the superior temporal gyrus lateral and rostrolateral to PL and AL; and regions of prefrontal cortex that receive inputs from auditory cortex. There were several major findings: 1. Best frequencies were most clearly determined for neurons within a densely myelinated strip of cortex on the lower bank and lip of the lateral sulcus. We divided this strip into three fields, A-I, R, and RT, although an alternative interpretation that A-I and R are parts of a single field remains tenable. In some cases, isofrequency contours appeared to continue uninterrupted across fields A-I and R, with lower frequencies represented laterally and higher frequencies represented deeper in the sulcus. In other cases, there was a tendency for high frequencies to be represented caudally and medially, and low frequencies laterally in A-I and rostrally in R, with partial discontinuity in the isofrequency contours. A reversal of the tonotopic gradient appeared in RT with a common low-frequency representation at the caudal border with R, and progressively higher frequencies encountered rostrally. Of the three fields, A-I appears slightly more myelinated than R, and RT slightly less than R. The distinctiveness of the three fields is further demonstrated by the patterns of connections. In particular, A-I and RT are both interconnected with R, but not with each other. Connections between A-I and R are between tonotopically matched locations. 2. A narrow 2-3 mm wide band of cortex lateral to A-I, R, and RT was also responsive to auditory stimuli, but typically neurons were more difficult to activate, and best frequencies were more difficult to determine. No distinctions in myeloarchitecture or CO activity were obvious.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

PubMed1992

Segregated thalamocortical pathways to inferior parietal and inferotemporal cortex in macaque monkey.

Inferior parietal and inferotemporal cortex, which process different aspects of visual information through largely segregated pathways from the visual cortex, both receive thalamic afferents from the pulvinar complex. We examined the topography of pulvinar projections to these two cortical regions by placing multiple injections of different tracers (fluorescent dyes, horseradish peroxidase) in the inferotemporal and inferior parietal cortex of macaque monkeys. The patterns of label observed after injections in inferotemporal gyrus indicate that area TEO and the ventral part of area V4 receive a major input from the ventral part of the lateral pulvinar (PuLv) while area TE has strong connections with the caudal pole of the medial pulvinar (PuM) and only minor connections with PuLv. In contrast, injections in the caudal inferior parietal cortex demonstrate that area PGc, on the lateral surface of the inferior parietal gyrus, and area POa, in the ventral bank of intraparietal sulcus, receive strong projections from PuM and the adjacent fringe of the dorsal part of the lateral pulvinar (PuLd). Paired injections of two different tracers in the inferotemporal and inferior parietal cortex of the same hemisphere revealed a nearly complete segregation of the two populations of labeled neurons in the pulvinar, with only a small region of overlap in PuM, close to the PuM/PuLd border. These results demonstrate a clear separation of the thalamic afferents to the inferior parietal and inferotemporal cortex which parallels the separation of prestriate afferents to these two cortical territories (Morel & Bullier, 1990).

Afferent Pathways↗

PubMed1992

Biochemical and pharmacological characterization of serotonin-O-carboxymethylglycyl[125I]iodotyrosinamide, a new radioiodinated probe for 5-HT1B and 5-HT1D binding sites.

There is a lack of radioactive probes, particularly radioiodinated probes, for the direct labeling of serotonin-1B (5-HT1B) and serotonin-1D (5-HT1D) binding sites. Serotonin-O-carboxymethylglycyltyrosinamide (S-CM-GTNH2) was shown previously to be specific for these two subtypes; we, therefore, linked a 125I to its tyrosine residue. Biochemical and pharmacological properties of S-CM-G[125I]TNH2-binding sites were studied by quantitative autoradiography on rat and guinea pig brain sections. S-CM-G[125I]TNH2 binding is saturable and reversible with a KD value of 1.3 nM in the rat and 6.4 nM in the guinea pig. Binding is heterogeneous, paralleling the anatomical distribution of 5-HT1B sites in the rat and of 5-HT1D sites in the guinea pig. The binding of 0.02 nM S-CM-G[125I]TNH2 was inhibited by low concentrations of 5-HT, S-CM-GTNH2, CGS 12066 B, 5-methoxytryptamine, and tryptamine in both species. Propranolol inhibited the radioligand binding with a greater affinity in the rat than in the guinea pig. Conversely, 8-hydroxy-2-(di-n-propylamino)tetralin inhibited S-CM-G[125I]TNH2 binding with a greater affinity in the guinea pig than in the rat. Other competitors, specific for 5-HT1C, 5-HT2, 5-HT3, and adrenergic receptors, inhibited S-CM-G[125I]TNH2 binding in rat and guinea pig substantia nigra and in other labeled structures known to contain these receptors, but only at high concentrations. S-CM-G[125I]TNH2 is then a useful new probe for the direct study of 5-HT1B and 5-HT1D binding sites.

Animals↗

PubMed1991

A new 5-hydroxy-indole derivative with preferential affinity for 5-HT1B binding sites.

The affinities of several 5-hydroxy-indole derivatives for serotonin-1 (5-HT1) binding site subtypes, labeled with 2 nM [3H]5-HT, were assessed by quantitative autoradiography on rat brain sections. The results obtained with known ligands, namely 5-hydroxytryptamine (5-HT), 5-methoxytryptamine (5-Me-OT), 5-methoxy-N,N- dimethyl-tryptamine (5-Me-ODMT), 5-hydroxy-N,N-dimethyl-tryptamine (bufotenine) and 8-hydroxy-2-[di-N-propylamino]tetralin (8-OH-DPAT) demonstrate the reliability and the advantages of this technique for pharmacological studies. Novel serotonin derivatives were synthesized by carboxymethylation of the hydroxyl group. One of those new ligands, serotonin-O-carboxy-methyl- glycyl-tyrosinamide (S-CM-GTNH2), inhibited 2 nM [3H]5-HT binding to the substantia nigra with an IC50 of 22.4 nM, a value which is 22 times lower than that found in the dentate gyrus and choroid plexus. This demonstrates the preferential affinity of S-CM-GTNH2 for 5-HT1B versus 5-HT1A and 5-HT1C binding sites. S-CM-GTNH2 contains a tyrosine residue, which may be useful for the synthesis of a radioactive iodinated molecule and for the preparation of 'long-lasting ligands' linked through peptide bonds with a protein. These derivatives could be of great interest for ultrastructural and behavioral studies relevant to 5-HT1B sites.

Animals↗

PubMed1991

A study of human jaw movements deduced from scratches on occlusal wear facets.

In a previous investigation, scratches on tooth wear facets provided information about functional movements of the mandible in the occlusal range. Depending on the type of facet observed, two or three main directions were found. The aim now was to answer two questions: (1) how long does it take for a newly formed scratch to disappear? and (2) do the observed orientations of the scratches change over a long period of time? Eleven wear facets from lower first molars were analysed in four subjects with good natural dentition. Scratches recorded on cellulose replicas were observed under an interference microscope. The same wear facets were recorded one, two, three and six months later. From the photographs of the replicas, a sample of scratches was selected at random and their direction was measured. In the first part of the study, scratches absent at the time of the first observation appeared one month later; 87% of the new scratches had disappeared after one month. Ninety-six percent of the same group of scratches had disappeared after two months. In the second part of the study the angle made by each scratch with the sagittal plane was recorded. It was found that: (1) jaw movements in their occlusal phase can take any possible direction and (2) the distribution of the observed scratches was not random; preferential orientations exist and those present on the working facets are different from those on the non-working facets. Similar orientations were identified 6 months later.

Adult↗

PubMed1991

Pharmacological characterization of serotonin-O-carboxymethyl-glycyl-tyrosinamide, a new selective indolic ligand for 5-hydroxytryptamine (5-HT)1B and 5-HT1D binding sites.

The affinity of a new serotonin (S) derivative, serotonin-O-carboxymethyl-glycyl-tyrosinamide (S-CM-GTNH2), for the various 5-hydroxytryptamine (5-HT)1 receptor subtypes was tested using quantitative autoradiography on rat and guinea pig brain sections. In the rat, S-CM-GTNH2 is 57 and 24 times more potent at 5-HT1B sites (IC50 = 28 nM) than at 5-HT1A (IC50 = 1600 nM) and 5-HT1C sites (IC50 = 670 nM), respectively. In the guinea pig, the affinity of S-CM-GTNH2 for 5-HT1D sites (IC50 = 67 nM) is 21 times higher than at 5-HT1A sites (IC50 = 1400 nM). S-CM-GTNH2 shows a low affinity (less than 10 microM) for 5-HT2 and 5-HT3 binding sites. This new ligand is therefore highly specific for 5-HT1B and 5-HT1D binding sites and can be used to further characterize the involvement of these subtypes in physiological studies focusing particularly on behavioral effects.

Animals↗

PubMed1991

[Synthesis and pharmacological study of radioiodinated serotonin derivative specific of 5-HT1B and 5-HT1D binding sites of the central nervous system].

We describe here the synthesis of a new serotonin conjugate, S-CM-GTNH2, and its radioiodinated derivative. Quantitative autoradiographic studies on rat and guinea pig brain sections incubated with 2 nM [3H]5-HT showed a preferential affinity of S-CM-GTNH2 for 5-HT1B and 5-HT1D sites. Autoradiograms from brain sections incubated with 0.02 nM S-CM-G[125I]TNH2 showed a heterogeneous anatomical distribution of the labelling with high densities in regions rich in 5-HT1B or 5-HT1D binding sites, and with no labelling of those rich in 5-HT1A or 5-HT1C sites. The pharmacological profiles of the binding sites corresponded to those of 5-HT1B and 5-HT1D receptor subtypes. The radioligand S-CM-G[125I]TNH2 is a good probe for the study of these sites and will be used for their subcellular localization in electron microscopy.

Animals↗

PubMed1990

Prosomatostatin II processing is initiated in the trans-Golgi network of anglerfish pancreatic cells.

Anglerfish prosomatostatin II, the precursor of somatostatin-28 II, is produced in different cells from prosomatostatin I, by a cleavage at Arg73. Antibodies were raised against the carboxy-terminal [64-72] portion of the precursor II upstream from somatostatin-28 II sequence. These antibodies recognized only this epitope when unmasked from the entire precursor, allowing the detection of the [1-72] domain which was isolated from pancreatic islets extracts. The antibodies were used to monitor the peptide bond cleavage occurring at the carboxy terminus of Arg73 to generate somatostatin-28 II. Immunocytochemistry revealed labeling both in the vesicles budding from the trans-Golgi network and in the dense core granules. Together, these data support the conclusions that i) prohormone processing is initiated in the Golgi apparatus of the pancreatic islet cells; ii) the "non-hormonal" [1-72] amino-terminal domain of the precursor may be involved in some intra and/or extra-cellular function(s).

Animals↗

PubMed1990

An immunoenzymoassay for histamine.

The clinical diagnosis of allergies needs appropriate tools for the measurement of histamine release from leukocyte suspension of affected patients. In the last few years the established fluorometric procedure has been challenged by alternatives like histamine radioimmunoassays (RIA). Although measurements of histamine with the latter methods make this procedure more accessible as a diagnostic tool, further simplifications are always welcomed. A newly developed immunoenzymoassay for histamine is described in the present work and compared to a recent radioimmunoassay. Sensitivity and specificity are shown to be comparable in both procedures.

Acetylcholinesterase↗

PubMed1990

Neuropeptides from the sinus gland of the lobster Homarus americanus: Characterization of hyperglycemic peptides.

In order to characterize hyperglycemic peptides from the sinus gland of the lobster, Homarus americanus, a bioassay was developed with juvenile H. gammarus. This assay was used for determining the hyperglycemic activity of peptides perified by reversed-phase high-performance liquid-chromatography, from acidic extracts of sinus gland. The major peptides are eluted in three sets of two peptides. Among them, two pairs show hyperglycemic activity when assayed on lobster; when assayed on crayfish, three peptides are active. The less hydrophobic pair consists of basic peptides (pI: 8.7), with a MW of 8633 Da., determined by fast-atom bombardment mass spectrometry. The most hydrophobic pair consists of acid peptides (pI: 5.0), with a MW of 8577 Da. Amino acid composition of the hyperglycemic peptides shows strong homologies within each pair.

Amino Acids↗

PubMed1990

Recognition of imidazole and histamine derivatives by monoclonal antibodies.

The different ways of raising antibodies to histamine are reviewed. High affinity monoclonal antibodies could be raised only against derivatized histamine. Succinyl glycinamide derivatization provided the basis of an efficient radioimmunoassay. In this paper the molecular pattern and the thermodynamical properties of histamine recognition were thoroughly investigated. Only the neutral form and not the cationic form of imidazole was recognized. As expected, the ligand recognition increased, with improved structural homology to the immunogen. However, a detailed analysis revealed a zwitterionic effect whenever a carboxylic group was present on the side chain of the ligand.

Animals↗

PubMed1990

Anatomical segregation of two cortical visual pathways in the macaque monkey.

A number of lines of evidence suggest that, in the macaque monkey, inferior parietal and inferotemporal cortices process different types of visual information. It has been suggested that visual information reaching these two subdivisions follows separate pathways from the striate cortex through the prestriate cortex. We examined directly this possibility by placing injections of the retrograde fluorescent tracers, fast blue and diamidino yellow, in inferior parietal and inferotemporal cortex and examining the spatial pattern of cortical areas containing labeled cells in two-dimensional reconstructions of the cortex. The results of injections in inferotemporal cortex show that TEO receives afferents from areas V2, ventral V3, V3A, central V4, V4t, and DPL in prestriate cortex and from areas IPa, PGa, and FST in the superior temporal sulcus (STS). Area TEp receives afferents only from V4 in prestriate cortex and from IPa, PGa, and FST in the anterior STS. Area TEa receives no prestriate input and is innervated by IPa, PGa, FST, and TPO in the anterior STS. The results of injections in inferior parietal cortex demonstrate that POa receives afferents from dorsal V3, V3A, peripheral V4, DPL, and PO in prestriate cortex, from MST and *VIP and from IPa, PGa, TPO, and FST in anterior STS. Area PGc (corresponding to 7a) is innervated by PO, MST, and by TPO in the anterior STS. Examination of the two-dimensional reconstructions of the pattern of labeling after combined injections of fast blue and diamidino yellow in areas POa and TEO revealed that these areas are principally innervated by different prestriate areas. Only a small region, centered on area V3A and extending into V4 and DPL, contained cells labeled by either injection as well as a small number of double-labeled cells. In contrast, areas POa and TEO receive afferents from extensive common regions in the anterior STS corresponding to areas IPa, PGa, and FST. These results directly demonstrate that visual information from the striate cortex reaches inferior parietal and inferotemporal cortices through largely separate prestriate cortical pathways. On the other hand, both parietal and inferotemporal cortices receive common inputs from extensive regions in the anterior STS which map play a role in linking the processing occurring in these two cortical subdivisions of the visual system.

Amidines↗

PubMed1989

Xenopus laevis skin Arg-Xaa-Val-Arg-Gly-endoprotease. A highly specific protease cleaving after a single arginine of a consensus sequence of peptide hormone precursors.

Comparison of the precursor sequence for several peptide hormones of Xenopus laevis skin revealed a consensus sequence around a single arginine cleavage site which is 100% conserved on four residues Arg-Xaa-Val-Arg-Gly (RXVRG). A tetradecapeptide substrate (Asp-Val-Asp-Glu-Arg-Asp-Val-Arg-Gly-Phe-Ala-Ser-Phe-Leu-NH2) was used as a probe to purify and characterize the putative processing endoprotease. A hydrophobic enzyme was purified at least 9000-fold from Xenopus skin exudate by a four-step procedure. This highly specific activity cleaves the Arg-Gly bond and has no effect on the Arg-Xaa bond. It was strongly inhibited by divalent ion chelators, moderately by phenylmethylsulfonyl fluoride, aprotinin, and 1-tosylamide-2-phenylethyl chloromethyl ketone, but was insensitive to soybean trypsin inhibitor. Tetradecapeptide derivatives selectively modified on each of the amino acids of the consensus sequence demonstrated the relevance of this conserved pattern to endoprotease action. This enzyme, which we refer to as RXVRG-endoprotease, is proposed to be involved in the post-translational processing of pro-caerulein, promagainin, pro-xenopsin, pro-glycyl-leucine amide, and pro-levitide of X. laevis skin secretory granules.

Amino Acid Sequence↗

PubMed1989

Characterization of a somatostatin-28 generating metallo-endoprotease from rat brain cytosol.

Brain cytosol contains a neutral metallo-protease of about 80,000 which cleaves a substrate containing the site at which mammalian prosomatostatin is cleaved to generate somatostatin 28 in vivo. This represents a cleavage on the carboxyl side of a single arginine residue at an Arg-Ser bond. The enzyme was unable to cleave several other substrates containing single arginine residues or two substrates containing an Arg-Lys or Lys-Arg pair. When it was incubated with anglerfish pancreatic prosomatostatin, it produced significant quantities of a peptide which co-eluted with somatostatin 28 II. Based on the ability of this enzyme to cleave small and large substrates related to somatostatin, it is a potential candidate for the enzymes which cleaves prosomatostatin in vivo.

Amino Acid Sequence↗

PubMed1989

Characterization of an endoprotease from rat small intestinal mucosal secretory granules which generates somatostatin-28 from prosomatostatin by cleavage after a single arginine residue.

We have extracted, characterized, and partially purified an enzyme from secretory granules from rat small intestinal mucosa which cleaves a synthetic prosomatostatin substrate on the carboxyl side of a single arginine residue. This substrate Leu-Gln-Arg-Ser-Ala-Asn-Ser-NH2 contains the monobasic site at which mammalian prosomatostatin is cleaved in vivo to generate somatostatin-28. This activity was released from the granules by osmotic shock followed by extraction with 500 mM KCl. The enzyme had a molecular weight of about 55,000, a pH optimum of about 7.5, and a Km for the synthetic substrate of 20 microM. It was partially inhibited by diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride, iodoacetate, soybean trypsin inhibitor, and EDTA. It was also very sensitive to aprotinin (complete inhibition at 25 micrograms/ml) but was not inhibited by bestatin, pepstatin, or p-chloromercuribenzoate. This endoprotease was unable to cleave three small trypsin and kallikrein substrates (N alpha-benzoyl-L-arginine ethyl ester, N alpha-benzoyl-DL-arginine p-nitroanilide, and N alpha-benzoyl-L-arginine 7-amido-4-methylcoumarin). It was unable to cleave either the Arg-Asp bond in CCK 12 or the Arg-Glu and Arg-Met bonds of synthetic peptides corresponding to sequences of anglerfish prosomatostatin II situated upstream from the somatostatin-28 domain. These observations together suggest that adjacent amino acids play a role in determining the conformational specificity of the monobasic cleavage. This soluble enzyme was also able to cleave three synthetic substrates containing dibasic residues (Arg-Lys or Lys-Arg) on the carboxyl side of the arginine, although it did so less rapidly than at the monobasic cleavage sites. When incubated with partially purified prosomatostatin from anglerfish pancreas, significant quantities of somatostatin-28 II were produced. All these cleavages were completely blocked by preincubation with aprotinin. Although further work is required to clarify the physiological role of this enzyme, it appears, in view of its catalytic properties, this endoprotease could be involved in the conversion of prosomatostatin to somatostatin-28 in intestine mucosal secretory cells.

Amino Acid Sequence↗