Multiple intracellular effectors modulate physiological functions of the cloned somatostatin receptors

Florio, Tullio; Schettini, Gennaro

doi:10.1677/jme.0.0170089

Cited by 63 publications

(27 citation statements)

References 44 publications

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“…The localization of SSTR-1 in endothelial cells is consistent with the finding that removal of endothelial cells abolished the vascular effect of somatostatin (31,32). All five receptors are coupled to G-proteins and affect a number of distinct signal transduction pathways (33,34). All five receptors are also functionally coupled to inhibition of adenyl cyclase (35).…”

Section: Discussionsupporting

confidence: 84%

Effect of Somatostatin on Rabbit Isolated Coronary Arteries

Ruiz

Padilla

Tejerina

2002

Japanese Journal of Pharmacology

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ABSTRACT-Somatostatin analogues are capable of inhibiting vascular smooth muscle and endothelial cell proliferation. However, little is known about the effect of somatostatin on vascular responses in endothelium-denuded coronary arteries in vitro. The aim of this work was to determine whether or not somatostatin prevented the contractile response induced by 5-hydroxytryptamine and acetylcholine in endothelium-denuded rabbit coronary arteries. Somatostatin attenuated the contraction produced by 5-hydroxytryptamine in both proximal (PC) and distal coronary (DC) arteries (contraction induced by 10 -4 M 5-hydroxytryptamine was inhibited by 10 -6 M somatostatin by 90.8 ± 11.0% (P<0.001, n = 9) and by 46.2 ± 14.0% (P<0.05, n = 9) in DC and PC, respectively), but concentration-dependently decreased the contraction induced by U46619 (11a-epoxy-methanoprostaglandin F2=) only in PC arteries, suggesting that the response of PC and DC arteries to somatostatin were qualitatively different. Furthermore, we suggest that somatostatin may enhance acetylcholine-induced relaxation by combination of increasing endothelium-dependent relaxation (by a NO-dependent mechanism) and blocking contraction at the muscle level.Keywords: Somatostatin, Coronary artery, Acetylcholine, 5-Hydroxytryptamine, Nitric oxide Vascular diseases as well as surgical interventions such as coronary angioplasty induce endothelial denudation (1, 2) in coronary arteries. Loss of the endothelial layer alters vascular responses to certain agonists; thus 5-hydroxytryptamine and acetylcholine, which induce vasodilatation in normal coronary arteries, might be impaired or even turn into vasoconstriction in endothelium-denuded coronary arteries, leading to coronary spasm (1, 3, 4). In addition, thromboxane A2 released by platelets (5) is another candidate for the mediation of coronary vasospasm (6) since it is found in increasing concentration at the site of coronary arterial stenosis (7).Somatostatin (SRIF) is a neouroendocrine peptide (8) that exerts a wide range of physiological actions. However, the vascular effects of somatostatin are still unclear. A variety of studies have demonstrated species and regional differences in the blood flow responses to somatostatin. Thus, while in the rat superior mesenteric artery, octreotride (a somatostatin analogue) boosts vasoconstriction induced by a -agonists (9), in the vascular bed of cats, somatostatin showed opposite effects (10). On the other hand, we and others have shown that, although somatostatin has no effect on arteries kept under resting tension, it relaxes arteries precontracted with noradrenaline in vitro (11,12). Despite positive effects of somatostatin found in animal models of coronary restenosis, based on the antiproliferative effect of this peptide on both vascular smooth muscle (13) and endothelial cells (14, 15), little is known about the effect of somatostatin on vascular responses in endothelium-denuded coronary arteries. The purpose of this work was to determine whether or not somatostatin, in an 'in ...

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Section: Discussionsupporting

confidence: 84%

Effect of Somatostatin on Rabbit Isolated Coronary Arteries

Ruiz

Padilla

Tejerina

2002

Japanese Journal of Pharmacology

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“…35 S]GTPgS binding, MAP kinase activation and tyrosine phosphatase activity to name but a few (Florio & Schettini, 1996;Patel, 1999). However, discrepancies often occur between the effects of SRIF ligands at a given receptor subtype, depending on the cell line, binding test, or second messenger studied.…”

Section: Discussionmentioning

confidence: 99%

Comparison of functional profiles at human recombinant somatostatin sst₂ receptor: simultaneous determination of intracellular Ca²⁺ and luciferase expression in CHO‐K1 cells

Nunn

Cervia

Langenegger

et al. 2004

British J Pharmacology

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1 Somatostatin (somatotropin release inhibiting factor; SRIF) acts via five G protein-coupled receptors (sst 1 -sst 5 ) that modulate multiple cellular effectors. The aim of this study was to compare two functional effects of the human sst 2 receptor stably expressed in CHO-K1 cells in a single experiment using a duplex assay for intracellular calcium and serum response element (SRE)-driven luciferase expression. 2 Intracellular calcium was measured using a fluorometric imaging plate reader II (FLIPR II). SRIF-14 rapidly and transiently increased intracellular calcium with a pEC 50 of 8.7470.03 (n ¼ 52). At 5 h after FLIPR II measurements, luciferase expression was determined. SRIF-14 concentrationdependently increased luciferase expression (pEC 50 ¼ 9.0670.03, n ¼ 52). 3 Natural and synthetic agonist/antagonist ligands for SRIF receptors were tested in the duplex assay. Correlation of agonist potencies and efficacies between the two responses were significant (r 2 ¼ 0.83 and 0.90, pEC 50 and E max , respectively). 4 Pertussis toxin pretreatment reduced SRIF-14/octreotide-mediated intracellular calcium increases by 45-47% and luciferase expression by 95-98%. 5 Thapsigargin pretreatment abolished the SRIF-14/octreotide-mediated intracellular calcium increase but had no effect on luciferase expression. 6 In conclusion, SRIF stimulates an increase in intracellular calcium and SRE-luciferase expression via human sst 2 receptors in CHO-K1 cells.

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“…These data indicate that SDF1 activity requires the activation of a G-protein of the Gi/Go subfamily, and that its effects are responsive to inhibitory stimuli as observed in both normal pituitary and secreting adenomas. Interestingly, pertussis toxin was able to abolish both the stimulatory effects of SDF1 (Florio et al 2006) and the inhibitory effects of somatostatin (Florio & Schettini 1996). SDF1 was also a powerful mitogen for GH4C1 cells, with a statistically significant effect already evident at a concentration of 6 .…”

Section: Biological Effects Of Sdf1 In Pituitary Adenoma Cells: the Gmentioning

confidence: 97%

“…The observation that pertussis toxin reversed both the stimulatory effects of SDF1 and the inhibitory action of somatostatin, depends on the observation that CXCR4 and all the somatostatin receptors are coupled to a pertussis toxinsensitive G-protein. However, the opposite biological effects observed can be understood by the different intracellular signaling activated by the respective receptors (for review see Schettini 1996 andBajetto et al 2001a). For example, an opposite regulation of ERK1/2 activity was reported for CXCR4 (activation; Bajetto et al 2001b) and the somatostatin receptors (inhibition; Massa et al 2004).…”

Section: Biological Effects Of Sdf1 In Pituitary Adenoma Cells: the Gmentioning

confidence: 99%

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function

Barbieri¹,

Bajetto²,

Porcile³

et al. 2007

Journal of Molecular Endocrinology

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Chemokines are key factors involved in the regulation of immune response, through the activation and control of leukocyte traffic, lymphopoiesis and immune surveillance. However, a large number of chemokines and their receptors are expressed in central nervous system (CNS) cells, either constitutively or induced by inflammatory stimuli, playing a role in many neuropathological processes. Stromal cell-derived factor 1 (SDF1) is a chemokine whose extra-immunological localization and functions have been extensively studied. SDF1 and its receptor CXCR4 were identified in both neurons and glia of many brain areas, including the hypothalamus, as well as at the pituitary level. Importantly, SDF1 and CXCR4 expression is increased in brain tumors in which their activity induced tumor cell proliferation and brain parenchyma invasion. Despite their localization, to date very few reports addressed the role of CXCR4 and SDF1 in the modulation of the hypothalamus/pituitary axis and their possible involvement in the development of pituitary adenomas. In this review, we discuss previous literature data on the role of chemokines in normal and adenomatous pituitary cells, focusing on recent data from our group showing that CXCR4 activation controls proliferation and both prolactin and GH release in the pituitary adenoma cell line GH4C1 through a complex network of intracellular signals. Thus, the SDF1/CXCR4 system together with other chemokinergic ligand-receptor pairs, may represent a novel regulatory pathway for pituitary function and, possibly, be involved in pituitary adenoma development. These lines of evidence suggest that the inhibition of chemokine receptors may represent a novel pharmacological target for the treatment of pituitary adenomas.

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Multiple intracellular effectors modulate physiological functions of the cloned somatostatin receptors

Cited by 63 publications

References 44 publications

Effect of Somatostatin on Rabbit Isolated Coronary Arteries

Effect of Somatostatin on Rabbit Isolated Coronary Arteries

Comparison of functional profiles at human recombinant somatostatin sst₂ receptor: simultaneous determination of intracellular Ca²⁺ and luciferase expression in CHO‐K1 cells

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function

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Multiple intracellular effectors modulate physiological functions of the cloned somatostatin receptors

Cited by 63 publications

References 44 publications

Effect of Somatostatin on Rabbit Isolated Coronary Arteries

Effect of Somatostatin on Rabbit Isolated Coronary Arteries

Comparison of functional profiles at human recombinant somatostatin sst2 receptor: simultaneous determination of intracellular Ca2+ and luciferase expression in CHO‐K1 cells

Role of stromal cell-derived factor 1 (SDF1/CXCL12) in regulating anterior pituitary function

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Comparison of functional profiles at human recombinant somatostatin sst₂ receptor: simultaneous determination of intracellular Ca²⁺ and luciferase expression in CHO‐K1 cells