Functional somatostatin receptors on a rat pancreatic acinar cell line

Viguerie, Nathalie; Tahiri-Jouti, N.; Estève, Jean-Pierre; Clerc, Pascal; Logsdon, C. D.; Svoboda, Michal; Susini, C.; Vaysse, Nicole; Ribet, A

doi:10.1152/ajpgi.1988.255.1.g113

Cited by 33 publications

(26 citation statements)

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“…Pancreatic acinar cells, which do not synthesize SS but possess functional receptors for SS (48,58), may respond to SS produced in the pancreas by the D cells in the islets of Langerhans as well as to circulating SS.…”

Section: Resultsmentioning

confidence: 99%

“…These observations have led to the suggestion that this peptide has a physiologically important function in the regulation of normal cell growth and that it might be a negative regulator of pancreatic acinar cell proliferation in vivo. SS exerts its physiological actions by interacting with membrane-bound receptors (48,58), which are coupled to adenylate cyclase (43), K' channels (61), voltage-dependent Ca*' channels (62), and tyrosine phosphatase (12). In addition, several authors have shown that SS increases the guanylate cyclase activity in several tissues (11,17,54).…”

Section: Guanylate Cyclase Somatostatin Receptors Somatostatin Like-imentioning

confidence: 99%

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Somatostatin binding capacity, guanylate cyclase and tyrosine phosphatase activities during pancreatic proliferation in the rat induced by gastrectomy

et al. 1995

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Gastrectomy increased pancreatic growth and this effect was associated with an increase in the number of somatostatin-14 (SS) receptors (146% of control) without altering their affinity. SS increased guanylate cyclase activity twofold in pancreatic acinar membranes from gastrectomized rats. The gastrectomy decreased pancreatic SS-like immunoreactivity (SS-LI) content (55% of control levels) and tyrosine phosphatase activity (74% of control levels). Administration of proglumide (20 mg/kg, IF), a gastrin/cholecystokinin (CCK) receptor antagonist, suppressed the inhibitory effect of gastrectomy on basal tyrosine phosphatase activity and SS-LI content, which returned to control levels. Furthermore, proglumide suppressed the increase of the number of SS receptors and of SS-stimulated guanylate cyclase activity induced by gastrectomy. All this suggests that pancreatic acinar cell growth is associated with upregulation of SS receptors, which could represent a mechanism promoted by the cell to negatively regulate the mitogenic activity of pancreatic growth factors such as CCK. In addition, the results also suggest that the negative regulation of tyrosine phosphatase activity may be important in the events involved in the pancreatic hyperplasia observed after gastrectomy

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Section: Resultsmentioning

confidence: 99%

Section: Guanylate Cyclase Somatostatin Receptors Somatostatin Like-imentioning

confidence: 99%

Somatostatin binding capacity, guanylate cyclase and tyrosine phosphatase activities during pancreatic proliferation in the rat induced by gastrectomy

et al. 1995

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“…Functional receptors for substance P (Womack et al, 1985), CCK (Logsdon, 1986;Scemama et al, 1988), VIP and somatostatin (Viguerie et al, 1987(Viguerie et al, , 1988 have been reported to exist in AR4-2J cells. Stimulation of substance P receptors leads to an increase in amylase secretion, as confirmed in this work.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, CCK is reportedly able to increase or inhibit amylase secretion in AR4-2J cells (Scemama et al, 1988). Somatostatin receptors were found to be coupled to a Ni (Gj) protein and therefore on stimulation inhibit the VIP response (Viguerie et al, 1987(Viguerie et al, , 1988. Unless the relative density of these various receptors is established, it is not clear whether simultaneous stimulation of all receptors or Gproteins during the photodynamic action of SALPC would be expected to result in the inhibition or, as in normal cells, stimulation of amylase release (Matthews & Cui, 1989a, 1990.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic action of sulphonated aluminium phthalocyanine (SALPC) on AR4-2J cells, a carcinoma cell line of rat exocrine pancreas

Matthews

Cui²

1990

Br J Cancer

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Summary The photodynamic effects of sulphonated aluminium phthalocyanine (SALPC) have been compared on cultured AR4-2J cells of a pancreatic carcinoma cell line and on exocrine cells of the normal phenotype freshly isolated from the rat pancreas; a multi-channel perifusion system was used for this kinetic study in vitro. Whereas light alone or SALPC alone was without effect on either cell type, photon activation of cellularly-bound SALPC with light > 570 nm permeabilised the cells and caused an increase in amylase secretion from normal acinar cells but a dose-dependent inhibition (10' to 10-0 M) of amylase release from AR4-2J cells. In contrast, direct permeabilisation of the plasma membrane with digitonin, jg ml-', evoked a marked release of amylase from both types of cell. Elevation of [Ca2"]i by the ionophore A23187, 10-6 M, elicited secretion of amylase from normal cells but had little effect on AR4-2J cells. Finally, it was established that the differential photodynamic effects of SALPC on amylase release were not attributable to any topographical differences in the microanatomical organisation of normal or tumour-derived cells; furthermore, the structural integrity of normal and AR4-2J cells was maintained after the photodynamic action of SALPC. It is concluded that the generation of singlet oxygen is responsible for permeabilisation of both types of cell and that photon-activated SALPC has functionally distinct effects on the constitutive secretion of amylase of tumour cells and the regulated secretory pathway of normal cells. These observations may be important in the development of drugs with a selective photodynamic action on pancreatic tumour cells.

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“…Their performance was tested in vitro and in vivo using the well-characterized AR4-2J rat pancreatic cell line, 27 which exclusively expresses the SSTR2 subtype. 28 With this model, high clinical relevance can be expected because SSTR2 is the most abundant of all of the 5 SSTRs in human SSTR-expressing tumors 29 and because human and rat SSTR2 share 95% sequence homology.…”

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confidence: 99%

Neuroendocrine tumor targeting: Study of novel gallium‐labeled somatostatin radiopeptides in a rat pancreatic tumor model

Froidevaux

Eberlé

Christe

et al. 2002

Intl Journal of Cancer

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Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTRexpressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes 67 Ga and 68 Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suit- SSTRs are overexpressed by a variety of neuroendocrine tumors and frequently by tumors of the nervous system, 1-4 making somatostatin analogs, such as OC, 5 attractive candidates for tumor targeting. 111 In-labeled DTPA-OC (OctreoScan) was the first radiopeptide routinely used in the clinic for imaging SSTR-positive tumors by scintigraphy. 6 -10 A new generation of somatostatin analogs, incorporating the macrocyclic chelator DOTA instead of DTPA, have been developed, which ensure better stability of the radiometal-peptide complex. After labeling with 90 Y (␤ --emitter 2.28 MeV, t 1 ⁄2 64.1 hr) or 111 In (␥-emitter, Auger-and conversionelectron emitter, 0.5-245 keV, t 1 ⁄2 67.9 hr), they showed improved biodistribution and tumor uptake in animal models [11][12][13] and their clinical utility as diagnostic and therapeutic tools was confirmed in patients. 14 -18 These findings prompted us and others to develop somatostatin analogs suitable for PET, which offers higher sensitivity and resolution than SPECT, making it possible to visualize very small metastatic lesions, including tumor deposits in regional draining lymph nodes. Several strategies have been studied to develop a somatostatin analog-based PET tracer using different positronemitting radionuclides. Wester et al. 19 successfully labeled OC with 18 F, but despite specific accumulation in the tumor, this radioligand was of limited clinical application, owing to fast tumor washout, high liver uptake and, hence, insufficient visualization of abdominal tumors. Various 64 Cu-labeled somatostatin analogs were synthesized which showed favorable biodistribution in animal models 20,21 and good performance for PET imaging in patients; 22 however, the use of 64 Cu relies on the availability of a cyclotron.Another interesting positron emitter is 68 Ga (t 1 ⁄2 68 min, ␤ ϩ 88%), which is produced by a 68 Ge/ 68 Ga generator available at most PET centers and is not dependent on a cyclotron. Gallium as radiometal is of even broader interest in nuclear medicine because it is also available as 67 Ga (t 1 ⁄2 78 hr), which is not only a ␥-emitter useful for tumor diagnosis (␥-camera scintigraphy, SPECT) but also an emitter of Auger (0.1-8 keV) and conversion (80 -90 keV) electrons, which makes it attractive for internal radiotherapy. 23 The radiotoxicity of 67 Ga has been demonstrated in vitro in a lymphoma cell line 24 and myeloid leukemic blasts. 25 The use of a low-energy emitter might increase the therapeutic index because most of the electrons deposit their energy within the target, i.e., the tumor, thereby min...

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Functional somatostatin receptors on a rat pancreatic acinar cell line

Cited by 33 publications

References 0 publications

Somatostatin binding capacity, guanylate cyclase and tyrosine phosphatase activities during pancreatic proliferation in the rat induced by gastrectomy

Somatostatin binding capacity, guanylate cyclase and tyrosine phosphatase activities during pancreatic proliferation in the rat induced by gastrectomy

Photodynamic action of sulphonated aluminium phthalocyanine (SALPC) on AR4-2J cells, a carcinoma cell line of rat exocrine pancreas

Neuroendocrine tumor targeting: Study of novel gallium‐labeled somatostatin radiopeptides in a rat pancreatic tumor model

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