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P Leroux

Publications and source records attributed to P Leroux.

At least 37 records · Page 2Linked to original sources
PubMed1997

Tracheobronchopathia osteochondroplastica presenting at the time of a difficult intubation.

Tracheobronchopathia osteochondroplastica (TO) is a rare and usually benign disorder affecting the trachea and occasionally the bronchi. We describe the case of a 46-year-old woman who was discovered to have TO at the time of a difficult intubation. This case was also unusual since the patient had presented no previous symptoms despite the presence of extensive endotracheal and bronchial lesions. The incidence of TO appears to be underestimated in the literature in view of the fact that it is usually benign. However, a more accurate estimate of its true prevalence may become available through the use of bronchoscopy and computerized tomographic scanning.

Bone and Bones↗
PubMed1997

Differential expression of multiple somatostatin receptors in the rat cerebellum during development.

The present study describes the expression pattern of somatostatin receptor genes during the development of rat cerebellum. Characterization of somatostatin receptors was carried out by binding studies using receptor subtype-selective ligands in the germinative epithelium and granule cell layer of the cerebellum from postnatal day 4 (P4) to P21 and in granule cell cultures. Quantitative reverse transcription-PCR carried out for the five receptor subtype mRNAs in cerebellar extracts showed that sst1 mRNAs are predominant at the end of gestation. A transient high expression of the sst2 gene was observed from P7 to P14. In parallel, high levels of binding sites sensitive to sst2 ligands were detected in the granule cell germinative epithelium and in granule cell cultures. sst3 mRNAs rapidly increased from P14 and became the predominant form at P21, but respective binding sites were not detected. Whereas sst4 mRNA levels were generally low, those of sst5 were nearly undetectable. Reverse transcription-PCR carried out in granule cell cultures revealed the relative abundance of sst mRNAs as follows: sst2 > sst1 > sst3 = sst4. sst5 mRNA was undetectable. The results show the expression of four somatostatin receptor genes, but only three receptors (sst1, sst4, and mainly sst2) were detected as binding sites during cerebellar development.

Animals↗
PubMed1997

RFLP markers show genetic recombination in Botryotinia fuckeliana (Botrytis cinerea) and transposable elements reveal two sympatric species.

Molecular markers revealed that Botryotinia fuckeliana (the teleomorph of Botrytis cinerea), a haploid, filamentous, heterothallic ascomycete, contained a large amount of intrapopulation genetic variation. The markers were used to determine the mode of reproduction and the population structure of this fungus. We did not detect any differentiation between isolates from different organs, collection dates, varieties of grape, or locations in the Champagne region of France, but two unexpected sympatric populations were identified. One group of isolates (transposa) contained the transposable elements Boty and Flipper; the other (vacuma) did not. These groups differed from one another for all the other markers. RFLP markers showed that there was genetic recombination in both groups of isolates. We conclude that there are two sympatric populations of B. fuckeliana in Champagne. One species (transposa) seems to be local and well adapted, while the other one (vacuma) is presumably a heterogeneous migrant population.

Alleles↗
PubMed1996

Distribution of somatostatin receptors in the adult human brainstem.

The neuropeptide somatostatin is widely distributed in the central nervous system of rat and human. Somatostatin-containing neurons are particularly abundant in the hypothalamus, the cerebral cortex and the limbic system. Somatostatin is also present in a number of discrete structures in the brainstem and spinal cord. The localization of somatostatin receptors provides valuable information regarding the possible roles of the peptide in the brain. In the present study, we have investigated the precise distribution of somatostatin binding sites in the human lower brainstem by quantitative autoradiography, using [125I- Tyr0,DTrp8]S14 as a radioligand. The tissues were collected from two individuals, aged 50 and 67 years, who had no antecedent of neurological disorders. The binding of the radioligand was visualized in 73 distinct anatomical regions of the medulla and pons and quantified by computer-assisted image analysis. Somatostatin binding sites were present in sensory nuclei, the highest densities being observed in the trigeminal complex (spinalis oralis and interpolaris) and in the nucleus (N.) tractus solitarii. Moderate to low densities of binding sites were detected in the N. vestibularis medialis and spinalis, and in the N. nervus trigemini sensibilis principalis. Many relay nuclei of the ascending somatosensory pathways contained moderate to high densities of binding sites: the inferior olivary complex, the N. arcuatus and the N. praepositus hypoglossi. Binding sites were also present in several motor nuclei such as the N. nervi hypoglossi, the N. dorsalis motorius nervi vagi, the N. nervi facialis and the N. nervi abducentis. Moderate to low concentrations of binding sites were detected in nuclei related to the reticular formation including the N. raphae pallidus, the N. parabrachialis and the N. supratrochlearis. The N. locus coeruleus exhibited a very high concentration of somatostatin binding sites in both individuals. The present data, together with previous studies on the distribution of somatostatin-immunoreactive fibers in the human brainstem, suggest that somatostatin may be involved in (i) sensory processes including vestibular sensitivity, somatosensoriality and proprioception, (ii) sleep-waking cycle and arousal and (iii) control of various neurovegetative functions including regulation of cardiovascular and respiratory activities as well as gastric acid secretion.

Aged↗
PubMed1996

Anatomical distribution of somatostatin receptors in the brainstem of the human fetus.

The distribution of somatostatin binding sites was studied in the pons and medulla oblongata of three human fetuses (gestional ages 26, 28 and 30 weeks). The study was carried out by in vitro quantitative autoradiography using either [125I-Tyr0,D-Trp8]somatostatin-14 or [125I-Tyr11]somatostatin-14 as radioligands. Somatostatin binding sites were observed in a number of nuclei subserving sensory, motor or integrative functions within the pons and medulla. In addition, discrete tracts also contained significant amounts of binding sites. Among structures involved in sensory processes, a high density of binding sites (40-60 fmol/ mg wet tissue) was measured in the dorsal cochlear nucleus and in the nucleus tractus spinalis trigemini caudalis. Moderate to high levels of binding sites (30-40 fmol/mg wet tissue) were detected in the other sensory cranial nerve nuclei. A moderate density of sites (15-30 fmol/mg wet tissue) was measured in most motor nuclei, the highest concentrations being observed in the dorsal motor nucleus of the vagus nerve, the facial nucleus, the hypoglossal nucleus and the nucleus ambiguus. The griseum pontis and the nucleus corporis pontobulbaris contained very high (> 60 fmol/mg wet tissue) and high concentrations of somatostatin binding sites, respectively, while the other relay nuclei contained low to moderate levels of binding. In monoaminergic nuclei, very high and moderate to high concentrations of somatostatin binding sites were measured in the nucleus locus coeruleus and in its dorsal subnucleus, respectively. Moderate densities of sites were detected in the ventral subnucleus of the nucleus locus coeruleus and in the different parts of the raphe. In the white matter, low levels of binding were measured in the inferior cerebellar peduncle, the lateral and median lemnisci and the tractus solitarius. Conversely, moderate to high concentrations of somatostatin binding sites were measured in the median and superior cerebellar peduncles. The pyramis contained a very high density of recognition sites. A marked heterogeneity in the density of binding sites was observed within a few structures particularly in the medial accessory olivary of nucleus and the medial longitudinal fasciculus. Selective ligands were used to determine the pharmacological profile of the [Tyr11]somatostatin-14 binding sites in various brainstem regions. In the dorsal cochlear nucleus and the pyramis, all somatostatin binding sites belonged to the SSA subtype. Conversely, in the lateral paragigantocellular nucleus, all somatostatin binding sites belonged to the SSB subtype. The other regions studied contained various proportions of SSA and SSB subtypes. In conclusion, the present study shows that high concentrations of somatostatin receptors are present in many regions of the human fetus brainstem. These data support the concept that somatostatin could be involved in the maturation of brain structures.

Age Factors↗
PubMed1995

Transient expression of somatostatin receptors in the brain during development.

The study of somatostatin receptors by means of autoradiography in tissue sections revealed high densities of binding sites in the immature central nervous system. In rat cerebral cortex, the receptors are present in the intermediate zone and in association with cells migrating through the cortical plate. Somatostatin receptors in the intermediate zone of fetuses and in the cortical plate of postnatal rats exhibit high and low affinities respectively for the somatostatin analogue MK 678. In the rat cerebellum, the external granule cell layer, a germinal matrix containing interneuron precursors, contains a high density of receptors. These receptors exhibit high affinity for MK 678 throughout the period of cell multiplication. In granule cell cultures from eight-day-old rats, MK 678, octreotide and somatostatin are able to inhibit cAMP formation induced by forskolin or pituitary adenylyl cyclase-activating polypeptide. Somatostatin reduces the intracellular Ca2+ concentration in cultured granule cells; this response desensitizes rapidly. These results suggest that the somatostatin receptors in the external granule cell layer are type 2 receptors (sstr2). A low density of receptors with low affinity for MK 678 was also detected in the external granule cell layer and in the granule cell layer of neonatal rats. In adult rats the cerebellum is devoid of somatostatin receptors. These observations indicate that somatostatin probably exerts morphogenetic activities through different receptor types in several structures of the central nervous system.

Animals↗
PubMed1995

Characterization of the somatostatin receptor subtype in a bronchial carcinoid tumor responsible for Cushing's syndrome.

Small ACTH-secreting carcinoid tumors responsible for Cushing's syndrome are often difficult to localize using available radiological investigations. Somatostatin receptors have been found in about 90% of carcinoid tumors studied, leading to a new approach for the localization of tumors or metastasis by using radiolabeled somatostatin analogs. We report a case of Cushing's syndrome due to an ACTH-secreting bronchial carcinoid tumor, completely suppressible with octreotide treatment and evidenced by body scintigraphy with 111In-labeled pentreotide. After removal, which led to patient recovery, the tumor was studied in vitro. In situ hybridization, using a complementary DNA probe, revealed POMC messenger ribonucleic acid in a subpopulation of tumor cells. These cells were labeled by immunochemistry using an antiserum directed against ACTH. Confocal laser scanning microscopy analysis showed that the ACTH-immunoreactive peptide was sequestered in secretory granules. Autoradiographic labeling using [125I-Tyrzero,D-Trp8]somatostatin-14 demonstrated the presence of somatostatin-binding sites in the whole tumor tissue. The relative affinities of various selective somatostatin analogs and the ability of GTP to inhibit radioligand binding suggested that the receptor expressed in the tumor cells belonged to the SSTR-2 subtype.

Adult↗
PubMed1994

Pharmacological characterization of somatostatin receptors in rat cerebellar nuclei.

Rat cerebellar nuclei contain somatotropin release-inhibiting factor (SRIF) receptors that bind [125I][Leu8,D-Trp22,Tyr25]SRIF-28 but do not bind [125I][Tyr0,D-Trp8]SRIF-14. The aim of the present study was to investigate the pharmacological profile of these receptors by means of binding experiments on tissue sections and quantitative autoradiography. Competition experiments indicated the presence of a single class of [125I][Leu8,D-Trp22,Tyr25]SRIF-28 binding sites in the lateral cerebellar nuclei, showing similar affinities for SRIF-14 and SRIF-28, but low affinity for short-chained analogs. The IC50 values for somatostatin analogs to compete with the binding of [125I][Leu8,D-Trp22,Tyr25]SRIF-28 in the lateral cerebellar nuclei ranked as follows: [Leu8,D-Trp22,Tyr25]SRIF-28 approximately SRIF-14 approximately SRIF-28 < CGP 23996 < D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2 (BIM 23052) < SMS 201-995 approximately N-Ahep-(7-10)SRIF-14-Bzl << MK 678 < D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2 (BIM 23056) < D-Phe-c[Cys-Tyr-D-Trp-Lys-Abu-Cys]Nal-NH2 (NC 8-12). Optimum binding of [125I][Leu8,D-Trp22,Tyr25]SRIF-28 did not require divalent cations, and was partly inhibited by guanosine 5' triphosphate. It appears from this study that the rat lateral cerebellar nuclei contain a pure population of receptors exhibiting the same binding characteristics as the recently cloned sstr1 somatostatin receptor. These nuclei could thus provide a useful model in which to investigate the characteristics of native sstr1.

Amino Acid Sequence↗
PubMed1994

Quantitative autoradiographic study of somatostatin receptors in the adult human cerebellum.

The evolution of the distribution and density of somatostatin receptors was studied in the human cerebellum during ageing. The brain tissues were collected 3-30 h after death from 20 individuals aged from 28 to 86 years. In vitro autoradiographic experiments were performed on blocks of vermis and of right and left cerebellar hemispheres, using [125I-Tyr0,DTrp8]S14 as a radioligand. In the vermis, the mean concentrations of somatostatin receptors in the molecular layer, the granular layer and the medulla were 140 +/- 9, 150 +/- 22 and 61 +/- 13 fmol/mg proteins, respectively. For each individual, the density of sites in the two lateral lobes was similar. The mean concentrations of somatostatin receptors in the molecular layer, the granular layer and the medulla were 152 +/- 17, 190 +/- 20 and 56 +/- 11 fmol/mg proteins, respectively. The mean level of somatostatin receptors and the type of distribution of the receptors were not correlated to the age of the patients. Different distribution patterns of somatostatin receptors were noted among the patients studied. In the majority of patients (11/20), the density of somatostatin receptors was higher in the granular layer than in the molecular layer. Conversely, in four patients, the density of somatostatin receptors was higher in the molecular layer. The other individuals exhibited similar concentrations of somatostatin receptors in the granular and molecular layers. The present study indicates that the adult human cerebellum contains a high concentration of somatostatin receptors (> 100 fmol/mg proteins) and that the receptor level does not decline during ageing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Somatostatin and pituitary adenylate cyclase-activating polypeptide (PACAP): two neuropeptides potentially involved in the development of the rat cerebellum.

Somatostatin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been originally isolated from the ovine hypothalamus on the basis of their hypophysiotropic activities. There is now evidence that somatostatin and PACAP may play a role in the development of the central nervous system, particularly in the cerebellum. High concentrations of somatostatin and somatostatin receptors have been detected in the rat cerebellum during the first two postnatal weeks. Somatostatin binding sites are associated with a germinative matrix, the external granule cell layer, which generates the majority of the interneurons of the cerebellum. By using immature granule cells in primary culture, we could demonstrate that somatostatin binding sites are actually expressed by neuroblasts and correspond to authentic receptors negatively coupled to adenylate cyclase. Concurrently, studies on the distribution of PACAP receptors in the immature rat cerebellum showed the presence of a high concentration of binding sites in the external granule cell layer during the first two postnatal weeks. Pharmacological characterization of these binding sites showed that they correspond to type I PACAP receptors positively coupled to adenylate cyclase. The concomitant and transient expression of somatostatin and PACAP receptors by cerebellar neuroblasts in the external granule cell layer suggests that the two neuropeptides may be involved in the regulation of multiplication, migration and/or differentiation of neuroblasts. This hypothesis is also supported by the actions of somatostatin and PACAP on various transduction systems. In particular, the opposite effects of the two neuropeptides on adenylate cyclase activity suggest that somatostatin and PACAP may exert antagonistic actions.

Animals↗
PubMed1993

Quantitative autoradiography of somatostatin receptors in the rat limbic system.

The distribution of somatostatin receptors (SRIF-R) was analyzed in the limbic system of the adult rat by in vitro autoradiography with [125I-Tyr0,DTrp 8]S14 as a radioligand. Precise quantification of the density of binding sites, at 0.2 mm intervals throughout the different areas revealed a marked heterogeneity of labeling in most structures. In particular, SRIF-R were concentrated in the basal (104.4 +/- 3.3 fmol/mg proteins) and basolateral amygdaloid nuclei (94.8 +/- 4.3 fmol/mg proteins), and in the nucleus of the lateral olfactory tract (121.6 +/- 2.4 fmol/mg proteins), whereas moderate densities were detected in the amygdalo-hippocampal nucleus (76.4 +/- 2.8 fmol/mg proteins). The medial (41.3 +/- 1.9 fmol/mg proteins) and the central (24.0 +/- 1.4 fmol/mg proteins) amygdaloid nuclei contained lower SRIF-R concentrations. It appears from these observations, in the light of the anatomical pathways of the amygdala, that intra-amygdalian SRIF-containing neurons project to the amygdalo-hippocampal nucleus, and that SRIF-R in the basolateral complex are the target of afferents from limbic cortical areas. SRIF-R were detected at different levels of the hippocampal formation but their distribution was more restricted than that of SRIF-containing fibers. The maximal density of sites was detected in the ventral and dorsal parts of the subiculum (115.0 +/- 3.4 and 87.0 +/- 2.8 fmol/mg proteins, respectively) and in the parasubiculum (100.1 +/- 5.4 fmol/mg proteins). In Ammon's horn, the stratum oriens and stratum radiatum of the CA1 field were the only sites enriched in SRIF-R (74.1 +/- 2.0 and 74.6 +/- 1.9 fmol/mg proteins, respectively). The apparent lack of receptors in the pyramidal cell layer indicated that, in Ammon's horn, SRIF is involved in intra-hippocampal communication. Low levels of receptors were found in the hippocampal CA2 and CA3 fields. SRIF-R in the dentate gyrus were mainly concentrated in the molecular layer (57.3 +/- 1.2 fmol/mg proteins). A very high density of sites was also observed in the entorhinal cortex (up to 123.1 +/- 1.5 fmol/mg proteins). A clear mismatch between SRIF and SRIF-R was detected in the septum and the habenula. In the profound layers of the cingulum and retrosplenial cortex, a heterogeneous distribution of SRIF-R was observed. High concentrations of sites were detected in the rostral zone of the cingulate cortex (93.4 +/- 2.0 fmol/mg proteins) while the posterior cingulate only exhibited moderate concentrations of sites (66.5 +/- 0.7 fmol/mg proteins).(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗
PubMed1993

Dose-effect and evidence of escape of inhibition after indomethacin treatment in a synchronized model of bone resorption.

We previously showed that cyclooxygenase inhibition by indomethacin (7.5 mg/kg/d) prevented resorption in a model of synchronized remodeling. In the present paper, we (i) tested the effectiveness of three doses of indomethacin (2, 4, 7.5 mg/kg/d) in this model, and (ii) verified whether indomethacin action was sustained in time. For that purpose, on day 6 after induction, untreated controls were compared with a group treated for six days with indomethacin (7.5 mg/kg/d), and an interrupted treatment group (4 days indomethacin + 2 days free). Indomethacin inhibited resorption and total number of osteoclasts in a dose-dependent manner. In the second experiment in the discontinued group, the resorption and total number of osteoclasts were similar to sham-treated animals. Indomethacin was still effective in the continuous treatment group; however, resorption was distinctly higher than in the rats treated for four days. These data indicate that despite cyclooxygenase inhibition, another metabolic pathway started resorption. The stoppage of prostanoid inhibition permitted the rapid and complete restoration of resorption.

Animals↗
PubMed1993

Localization and characterization of PACAP receptors in the rat cerebellum during development: evidence for a stimulatory effect of PACAP on immature cerebellar granule cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are abundant in the brain and particularly in the cerebellum of adult rats. In contrast, the occurrence of PACAP binding sites has not been investigated during ontogenesis. The aim of the present study was to determine the distribution and biochemical characteristics of PACAP binding sites in the rat cerebellum during postnatal development, and to examine the effect of PACAP on immature cerebellar granule cells. Autoradiographic studies revealed that PACAP binding sites are transiently expressed in a germinative matrix of the cerebellar cortex, the external granule cell layer, and in the medulla, from postnatal days 8 to 25. A population of PACAP binding sites persisted in the internal granule cell layer in the mature cerebellum. Emulsion-coated cytoautoradiography, performed on cultured immature granule cells from eight-day-old rat cerebellum, demonstrated that transient PACAP binding sites are expressed by cerebellar immature granule cells. Biochemical characterization of binding revealed the occurrence of two classes of PACAP recognition sites exhibiting, respectively, high (Kd = 0.39 +/- 0.08 nM) and low (Kd = 21.2 +/- 9.4 nM) affinity for PACAP27. The two naturally occurring forms PACAP38 and PACAP27 were equipotent in competing for [125I]PACAP27 binding. In contrast, the [Des-His1]PACAP38 analog was eight times less efficient and vasoactive intestinal polypeptide only induced weak displacement of the binding. Exposure of cultured immature granule cells to PACAP27 resulted in a dose-dependent stimulation of the production of cAMP, indicating that PACAP binding sites represent authentic receptors positively coupled to adenylate cyclase. These results show that PACAP receptors are actively expressed in the cerebellum of rats during postnatal development. The presence of functional PACAP receptors in the external granule cell layer suggests that PACAP may play a role in the control of proliferation and/or differentiation of granule cells.

Adenylyl Cyclases↗
PubMed1993

Localization of somatostatin receptors in subcortical visual centres of the rat during development. Effect of neonatal enucleation on the expression of somatostatin receptors.

Previous studies have shown that both somatostatin and somatostatin receptors are expressed in the visual system of the rat early during ontogenesis, suggesting that somatostatin plays a role in the development of visual functions. In the present study, we have examined the localization of somatostatin receptors in the lateral geniculate nucleus and the superior colliculus of the developing rat by autoradiography, and we have investigated the effect of neonatal enucleation on the density of receptors in young and adult animals. In the dorsal part of the lateral geniculate nucleus, somatostatin receptors were transiently expressed during the first two postnatal weeks, while in the ventral part, receptors were detected during the whole developmental period. In the superior colliculus, a high density of somatostatin receptors was measured before eye opening; thereafter the concentration of receptors decreased markedly in the whole structure to reach the adult level. Uni- or bilateral enucleation one day after birth only induced minor modifications of the expression of somatostatin receptors in the lateral geniculate nucleus and colliculus. Conversely, bilateral enucleation caused a significant reduction of the density of receptors in the inter-geniculate leaflet and the medial zone of the ventral lateral geniculate nucleus. Taken together, these results indicate that, in the relay nuclei, somatostatin receptors are not borne by retinal afferents. The presence of high densities of receptors in the lateral geniculate nucleus and superior colliculus during development suggests that somatostatin exerts trophic activities in these structures. In adult rat, somatostatin is probably involved in the modulation of visual information in the superior colliculus, but not in the dorsal lateral geniculate nucleus.

Amino Acid Sequence↗
PubMed1993

[Regulation of osteoclastic resorption by prostanoids in vivo].

Prostanoids, and particularly prostaglandins (PGs) E, are potent mediators of bone resorption. However the actual role(s) of these agents in osteoclastic resorption is (are) not yet known. In an attempt to approach the role of prostanoids in the events leading to resorption itself, we used two different animal models. We showed that indomethacin, an inhibitor of prostanoid biosynthesis, drastically reduced osteoclastic resorption at the dose of 7 mg/kg/d in the two models. This effect was dose-dependent as resorption inhibition increased by increasing the dose of indomethacin. However the effect was already significant at the lower dose (2 mg/kg/d). The total number of osteoclasts in the site was according by reduced, showing the involvement of the prostanoids in the events preceding and/or regulating the fusion of the mononucleated preosteoclasts into multinucleated osteoclasts. The calculation of the ratio active/inactive osteoclasts indicated that the activation (i.e. access to the bone surface) of the osteoclast, was prostanoid-dependent; indeed the ratio systematically decreased in the indomethacin-treated animals in the two models. We also observed that the inhibition was not sustained in time as resorption recovered, probably through the starting of PG-independent metabolic pathways. However this starting was rather slow and these pathways apparently were less affective than the PG-dependent ones since the intrinsic activity of the differentiated osteoclasts was significantly reduced.

Animals↗
PubMed1992

Somatostatin receptors are expressed by immature cerebellar granule cells: evidence for a direct inhibitory effect of somatostatin on neuroblast activity.

Somatostatin and somatostatin receptors are transiently expressed in the immature rat cerebellar cortex but virtually undetectable in the cerebellum of adults. Although somatostatin binding sites have been visualized during the postnatal period in the external granule cell layer, the type of cell that expresses somatostatin receptors has never been identified; thus, the potential function of somatostatin in the developing cerebellum remains unknown. In the present study, we have taken advantage of the possibility of obtaining a culture preparation that is greatly enriched in immature cerebellar granule cells to investigate the presence of somatostatin receptors and the effect of somatostatin on intracellular messengers on cerebellar neuroblasts in primary culture. Autoradiographic labeling revealed the occurrence of a high density of binding sites for radioiodinated Tyr-[D-Trp8]somatostatin-(1-14) on 1-day-old cultured immature granule cells. Saturation and competition studies showed the existence of a single class of high-affinity binding sites (Kd = 0.133 +/- 0.013 nM, Bmax = 3038 +/- 217 sites per cell). Somatostatin induced a dose-dependent inhibition of forskolin-evoked cAMP formation (ED50 = 10 nM), and this effect was prevented by preincubation of cultured immature granule cells with pertussis toxin. Somatostatin also caused a marked reduction of intracellular calcium concentration. These results show the presence of functionally active somatostatin receptors on immature granule cells. Our data suggest the possible involvement of somatostatin in the regulation of proliferation and/or migration of neuroblasts during the development of the cerebellar cortex.

Adenylyl Cyclases↗
PubMed1992

Somatostatin receptors in the human cerebellum during development.

The ontogeny of somatostatin receptors (SRIF-R) was studied in the human cerebellum from mid-gestation to the 15th month postnatal. The brains were collected 3-26 h after death, from 18 fetuses and infants, and from 4 adults aged from 48 to 82. SRIF-R were characterized by membrane-binding assay and their localization was determined by in vitro autoradiography. Both techniques were conducted with two radio-ligands: [125I-Tyr0, DTrp8]S14 and D-Phe-Cys-125I-Tyr-DTrp-Lys-Thr- ol (125I-SMS 204-090). Membrane-binding studies carried out with each radioligand showed the presence of a single population of saturable, high affinity binding sites. Neither were the Kd values for either ligand (assessed by Scatchard analysis) changed appreciably during development, mean Kd values being 0.36 +/- 0.04 nM and 0.56 +/- 0.11 nM for [125I-Tyr0,DTrp8]S14 and 125I-SMS 204-090, respectively. Although inter-individual fluctuations of the Bmax were observed, the concentration of SRIF-R in the cerebellum of fetuses and infants up to 8 months appeared to be at least 2- to 10-fold higher than in the adult cerebellum. No appreciable differences in the Bmax values were found using either radioligand. The highest density of SRIF-R was observed in the cerebellar cortex of fetuses, in particular in the external granule cell layer (EGC), where stem cells of the granule cells are generated and enter the differentiation process. A high density of SRIF-R also occurred in the internal granule cell layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗