Processing of receptor-bound somatostatin: internalization and degradation by pancreatic acini

Viguerie, Nathalie; Estève, Jean-Pierre; Susini, C.; Vaysse, N.; Ribet, A

doi:10.1152/ajpgi.1987.252.4.g535

Cited by 14 publications

(19 citation statements)

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“…It is tempting to speculate that the abrupt decrease in the concentration of somatostatin binding sites observed in the N. parabrachialis lateralis and the N. locus coeruleus during the perinatal period may be ascribed to neural and/or endocrine regulation of receptor gene expression. It has previously been shown that somatostatin inhibits the expression of its own receptors in anterior pituitary cells (Draznin et al, 1985;Mentlein et al, 1989), pancreatic acinar cells (Viguerie et al, 1987), and anterior pituitary tumor cells (Reisine and Axelrod, 1983;Heisler and Srikant, 1985). Therefore, the decrease in the density of somatostatin binding sites observed in the human brainstem nuclei during development might also result from downregulation of the receptors by endogenous somatostatin.…”

Section: Developmental Changes In the Density Of Somatostatin Bindingmentioning

confidence: 96%

Ontogeny of somatostatin binding sites in respiratory nuclei of the human brainstem

et al. 1997

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The ontogeny of somatostatin binding sites was studied in 16 respiratory nuclei of the human brainstem, from 19 postconceptional weeks to 6 months postnatal, by quantitative autoradiography using [(125)I-Tyr0,DTrp8]S14 as a radioligand. In the early gestational stages (19-21 postconceptional weeks), moderate to high concentrations of [(125)I-Tyr0,DTrp8]S14 binding sites were found in all nuclei, the highest density being measured in the locus coeruleus. From 19 weeks of fetal life to 6 months postnatal, a decrease in the density of labeling was observed in all nuclei. The most dramatic reduction in site density (80-90%) was found in the ventral part of the nucleus medullae oblongata lateralis and in the nucleus paragigantocellularis lateralis. A 70-80% decrease was detected in the dorsal part of the nucleus tractus solitarius, the nucleus nervi hypoglossi, the ventral part of the nucleus medullae oblongatae centralis, the nucleus ambiguus, the nucleus paragigantocellularis dorsalis, and the nucleus gigantocellularis, and a 60-70% decrease in the nucleus parabrachialis medialis, the ventrolateral and ventromedial parts of the nucleus tractus solitarius, and the nucleus praepositus hypoglossi. A 50-60% decrease was observed in the caudal part of the nucleus tractus solitarius, the nucleus dorsalis motorius nervi vagi, and the nucleus parabrachialis lateralis, whereas in the nucleus locus coeruleus, the concentration of recognition sites decreased by only 30%. The profiles of the decrease in site density differed in the various structures. In the majority of the nuclei, a gradual diminution of binding density was observed either throughout the developmental period studied or mainly during fetal life. Conversely, in two nuclei, i.e., the nucleus parabrachialis lateralis and the locus coeruleus, an abrupt decrease occurred around birth. The differential decrease in the density of somatostatin binding sites observed in respiratory nuclei during development, together with the observation that microinjection of somatostatin in some of these nuclei causes ventilatory depression and apnea, strongly suggests that the somatostatinergic systems of the human brainstem are involved in the maturation of the respiratory control.

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Section: Developmental Changes In the Density Of Somatostatin Bindingmentioning

confidence: 96%

Ontogeny of somatostatin binding sites in respiratory nuclei of the human brainstem

et al. 1997

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“…Complete purification of the three Bodipy-labeled peptides was easily achieved as the observed elution times of each HPLC fractions were clearly different (35,44,58, and 63 min for native SRIF and its ␣-, ⑀ 4 -, and ⑀ 9 -Bodipy analogs, respectively). Complete purification of the three Bodipy-labeled peptides was easily achieved as the observed elution times of each HPLC fractions were clearly different (35,44,58, and 63 min for native SRIF and its ␣-, ⑀ 4 -, and ⑀ 9 -Bodipy analogs, respectively).…”

Section: Molecular Characterization Of Fluorescent [D-trp 8 ]Srif Dermentioning

confidence: 99%

“…Several reports indicate that SRIF is internalized in pancreatic (34,35), hypophyseal (36,37,38), and human carcinoid tumor (39) Several reports indicate that SRIF is internalized in pancreatic (34,35), hypophyseal (36,37,38), and human carcinoid tumor (39) …”

mentioning

confidence: 99%

Differential Internalization of Somatostatin in COS-7 Cells Transfected with SST₁and SST₂Receptor Subtypes: A Confocal Microscopic Study Using Novel Fluorescent Somatostatin Derivatives¹

et al. 1997

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A growing body of evidence suggests that neuropeptide binding to G protein-linked receptors may result in internalization of receptor-ligand complexes, followed by intracellular mobilization and degradation of the ligand into its target cells. Because of discrepant results in the literature concerning the occurrence of such a mechanism for the tetradecapeptide somatostatin (SRIF), we have reinvestigated this question by comparing the binding and internalization of iodinated and fluorescent derivatives of the metabolically stable analog of SRIF, [D-Trp8]SRIF, in COS-7 cells transfected with complementary DNA encoding the sst1 or sst2A receptor subtype. A series of fluoresceinyl and Bodipy fluorescent derivatives of [D-Trp8]SRIF-14 was purified by HPLC, analyzed for purity by mass spectrometry, and tested for biological activity in a membrane binding assay. Of the six compounds tested, fluoresceinyl and Bodipy derivatives labeled in position alpha (fluo-SRIF) retained high affinity for SRIF receptors. COS-7 cells transfected with complementary DNA encoding either sst1 or sst2A receptors both displayed specific, high affinity binding of iodinated and fluo-SRIF. At 4 C, the labeling was confined to the cell surface in both cell types, as indicated by the fact that it was entirely removable by a hypertonic acid wash and assumed a pericellular distribution in the confocal microscope. At 37 C, the fate of specifically bound ligand varied markedly according to the type of receptor transfected. In cells encoding the sst1 receptor, approximately 20% of specifically bound ligand was recovered in the acid-resistant (i.e. intracellular) fraction. This fraction remained clustered at the periphery of the cell, suggesting that it was being sequestered either within or immediately beneath the plasma membrane. By contrast, in cells transfected with sst2A receptors, up to 75% of specifically bound ligand was recovered inside the cells, where it clustered into small endosome-like particles. These particles increased in size and moved toward the nucleus with time, suggestive of receptor-ligand complexes proceeding down the endocytic pathway. These results demonstrate that neuropeptides may be processed differently depending on the subtype of receptor expressed in their target cells and suggest that these different processing patterns may reflect different modes of sensitization/desensitization and recycling of the receptors, and thereby of transmembrane signaling.

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“…Thus although receptor-mediated internalization of the ligand is not thought to participate in the down-regulation of membrane SRIF-binding sites on tumorous cell lines (Presky & Schonbrunn, 1986), it may be involved in their autoregulation in normal pituitary tissue. This possibility is supported by the demonstration that sig¬ nificant (15%) internalization of membrane-bound SRIF occurs in normal rat anterior pituitary cells (Draznin, Sherman, Sussman et al 1985) and pan¬ creatic tissue (Viguerie, Esteve, Susini et al 1987) within 15-20 min of incubation, whereas receptormediated internalization of SRIF in tumorous cells is not rapidly induced (Presky & Schonbrunn, 1986). The rapid down-regulation of SRIF-binding sites in the chicken pituitary gland may, therefore, be similar li 11 tí°c Hĉ e Q.…”

Section: Homologous Regulation Of Srif-binding Sitesmentioning

confidence: 93%

Homologous and heterologous regulation of somatostatin-binding sites on chicken adenohypophysial membranes

Harvey

Baidwan²,

Attardo³

1990

Journal of Endocrinology

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Binding of 125I-labelled [Tyr1]-somatostatin (125I-[Tyr1]-SRIF) to pituitary caudal lobe membranes was suppressed in immature chickens 1 and 2 h after i.v. administration of unlabelled SRIF at concentrations of 1-100 micrograms/kg. In-vitro preincubation of chicken pituitary glands for 0.5-4.0 h with 0.1 mumol SRIF/l similarly reduced the binding of 125I-[Tyr1]-SRIF to caudal lobe membrane preparations. After a 4-h incubation in 0.1 mmol SRIF/l, the withdrawal of SRIF from the incubation media was accompanied 4 h later by a partial recovery in the binding of 125I-[Tyr1]-SRIF to pituitary membranes. Passive immunoneutralization of endogenous SRIF resulted in a prompt (within 1 h) and sustained (for at least 24 h) suppression of 125I-[Tyr1]-SRIF binding to pituitary membranes. The i.m. administration of cysteamine (300 mg/kg) to 12-week-old birds depleted hypothalamic SRIF stores and decreased the density of 125I-[Tyr1]-SRIF-binding sites in the caudal and cephalic lobes of the chicken pituitary gland. The reduction in SRIF content and in SRIF-binding sites occurred within 1 h of cysteamine administration and was maintained for at least 24 h. In 6-week-old birds, cysteamine (300 mg/kg) administration suppressed pituitary binding of 125I-[Tyr1]-SRIF for at least 5 days. Circulating concentrations of GH were markedly decreased 1 and 4 h after cysteamine injection, but not after 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

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Processing of receptor-bound somatostatin: internalization and degradation by pancreatic acini

Cited by 14 publications

References 0 publications

Ontogeny of somatostatin binding sites in respiratory nuclei of the human brainstem

Ontogeny of somatostatin binding sites in respiratory nuclei of the human brainstem

Differential Internalization of Somatostatin in COS-7 Cells Transfected with SST₁and SST₂Receptor Subtypes: A Confocal Microscopic Study Using Novel Fluorescent Somatostatin Derivatives¹

Homologous and heterologous regulation of somatostatin-binding sites on chicken adenohypophysial membranes

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Processing of receptor-bound somatostatin: internalization and degradation by pancreatic acini

Cited by 14 publications

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Ontogeny of somatostatin binding sites in respiratory nuclei of the human brainstem

Ontogeny of somatostatin binding sites in respiratory nuclei of the human brainstem

Differential Internalization of Somatostatin in COS-7 Cells Transfected with SST1and SST2Receptor Subtypes: A Confocal Microscopic Study Using Novel Fluorescent Somatostatin Derivatives1

Homologous and heterologous regulation of somatostatin-binding sites on chicken adenohypophysial membranes

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Differential Internalization of Somatostatin in COS-7 Cells Transfected with SST₁and SST₂Receptor Subtypes: A Confocal Microscopic Study Using Novel Fluorescent Somatostatin Derivatives¹