Heterooligomerization of human dopamine receptor 2 and somatostatin receptor 2

Baragli, Alessandra; Alturaihi, Haydar; Watt, Heather; Abdallah, Ali T.; Kumar, Ujendra

doi:10.1016/j.cellsig.2007.07.007

Cited by 116 publications

(49 citation statements)

References 53 publications

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“…Rocheville et al [26] illustrated that binding of quinpirole, the D2R receptor agonist, increased binding affinity of somatostatin by 3,000%. Recently, it was demonstrated that human D2R and SSTR-2 also operate as functional heterodimers following ligand stimulation with enhanced functional activity [1]. …”

Section: Discussionmentioning

confidence: 99%

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Expression of Somatostatin and Dopamine 2 Receptors in Neuroendocrine Tumours and the Potential Role for New Biotherapies

Srirajaskanthan¹,

Watkins

Marelli³

et al. 2009

Neuroendocrinology

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Introduction: Somatostatin and dopamine receptors are both G-protein-coupled receptors. Somatostatin receptor (SSTR) expression in neuroendocrine tumours has been well characterised, and there is evidence of dopamine receptor expression in neuroendocrine tumours. In this study, we examined expression of D2R, SSTR-2 and SSTR-5 using immunohistochemistry in patients with neuroendocrine tumours. Methods: Consecutive samples of formalin-fixed paraffin-embedded tumour tissue were available from 56 patients with a histologically confirmed diagnosis of neuroendocrine tumour (NET). The study population was divided into low-grade (n = 29), intermediate-grade (n = 18) and high-grade NET (n = 9). Immunohistochemical evaluation was performed for the expression of SSTR-2a, SSTR-5 and D2 receptors (D2R). Results: Both SSTR-2 and SSTR-5 were expressed in 100% of low-grade, 94.4% of intermediate-grade and 66.7% of high-grade NET. D2R was expressed in 93.1% of low-grade, 77.8% of intermediate-grade and 44.4% of high-grade tumours. Co-expression of all 3 receptors was present in 93.1% of low-grade tumours. There was an inverse correlation of SSTR-2 (r = –0.380, p < 0.005) and SSTR-5 (r = –0.472, p < 0.0001) with tumour grade. D2R was positively correlated with SSTR-2 (r = 0.269, p = 0.041) and SSTR-5 (r = 0.267, p = 0.045). Also, D2R expression was inversely correlated with grade of tumour (r = 0.395, p = 0.006). Octreoscan correlated with SSTR-2, SSTR-5 and D2R expression. Conclusion: D2R is expressed in the majority of low and intermediate grade tumours. It is co-expressed with SSTR-2 and SSTR-5 in the majority of cases. The advent of new chimeric molecules that bind both somatostatin and dopamine receptors may provide a new therapeutic option in the management of neuroendocrine patients.

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Section: Discussionmentioning

confidence: 99%

“…The somatostatin and dopamine systems constitute 2 major receptor networks that share similar structural features [1]. Both families of receptors are G-protein-coupled membrane receptors.…”

Section: Introductionmentioning

confidence: 99%

Expression of Somatostatin and Dopamine 2 Receptors in Neuroendocrine Tumours and the Potential Role for New Biotherapies

Srirajaskanthan¹,

Watkins

Marelli³

et al. 2009

Neuroendocrinology

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“…In this latter phenomenon, an interference with the b-arrestin system is probably involved (Grant et al 2008). Another possible explanation of the enhanced antiproliferative action of heterodimers (especially SSR/DR dimers) may be the increased D 2 R activity observed in the cell lines transfected with sstr 2 and D 2 R after the treatment with SRIF (Baragli et al 2007). Studies focused on signal transmission at the postmembrane level showed that SRIF/DA receptor activation (largely sstr 2 /D 2 R) may result in the phosphorylation of c-Jun N-terminal kinase(B) and inhibition of transcription of the cyclin Ki-67, resulting in growth arrest (Kidd et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…SSTR dimerization can be a ligand-dependent phenomenon, since natural SRIF and subtype-specific SRIF agonists have different effects on dimerization, leading to formation or, on the contrary, dissociation of SSTR dimers (Rocheville et al 2000a, Pfeiffer et al 2001, Patel et al 2002, Grant et al 2004a,b, 2008. SSTR homo-and heterodimerization also involve cellular events beyond the membrane, since it modifies SSTR internalization and trafficking (Baragli et al 2007), as well as signal transduction (Kidd et al 2008). SSTRs can also heterodimerize with other G-protein-coupled receptors, such as the m-opioid receptor (Pfeiffer et al 2002) and dopamine (DA) type 2 receptor (D 2 R; Rocheville et al 2000b, Baragli et al 2007.…”

Section: Introductionmentioning

confidence: 99%

“…SSTR homo-and heterodimerization also involve cellular events beyond the membrane, since it modifies SSTR internalization and trafficking (Baragli et al 2007), as well as signal transduction (Kidd et al 2008). SSTRs can also heterodimerize with other G-protein-coupled receptors, such as the m-opioid receptor (Pfeiffer et al 2002) and dopamine (DA) type 2 receptor (D 2 R; Rocheville et al 2000b, Baragli et al 2007.…”

Section: Introductionmentioning

confidence: 99%

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Somatostatin and dopamine receptor interaction in prostate and lung cancer cell lines

Arvigo¹,

Gatto²,

Ruscica³

et al. 2010

Journal of Endocrinology

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Somatostatin analogues inhibit in vitro cell proliferation via specific membrane receptors (SSTRs). Recent studies on transfected cell lines have shown a ligand-induced formation of receptor dimers. The aim of this study is 1) to evaluate the role of specific ligands in modulating receptor interactions in the androgen-dependent prostate cancer cell line, LNCaP, and in the non-small cell lung cancer line, Calu-6, by co-immunoprecipitation and immunoblot; and 2) to correlate the antiproliferative effect of these compounds with their ability in modulating receptor interactions. In LNCaP, we have demonstrated the constitutive presence of sstr 1 /sstr 2 , sstr 2 /sstr 5 , sstr 5 /dopamine (DA) type 2 receptor (D 2 R), and sstr 2 /D 2 R dimers. BIM-23704 (sstr 1 -and sstr 2 -preferential compound) increased the co-immunoprecipitation of sstr 1 /sstr 2 and significantly inhibited proliferation (K30 . 98%). BIM-23244 (sstr 2 -sstr 5 selective agonist) significantly increased the co-immunoprecipitation of sstr 2 /sstr 5 , and induced a K41 . 36% inhibition of proliferation. BIM-23A760, a new somatostatin/DA chimeric agonist with a high affinity for sstr 2 and D 2 R and a moderate affinity for sstr 5 , significantly increased the sstr 5 /D 2 R and sstr 2 /D 2 R complexes and was the most powerful in inhibiting proliferation (K42 . 30%). The chimeric compound was also the most efficient in modulating receptor interaction in Calu-6, increasing the co-immunoprecipitation of D 2 R/sstr 5 and inhibiting cell proliferation (K30 . 54%). However, behind BIM-23A760, BIM-53097 (D 2 R-preferential compound) also significantly inhibited Calu-6 proliferation (K17 . 71%), suggesting a key role for D 2 R in receptor cross talk and in controlling cell growth. Indeed, activation of monomeric receptors did not affect receptor co-immunoprecipitation, whereas cell proliferation was significantly inhibited when the receptors were synergistically activated. In conclusion, our data show a dynamic ligand-induced somatostatin and DA receptor interaction, which may be crucial for the antiproliferative effects of the new analogues.

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Cortistatins and Dopastatins

Albertelli¹,

Ferone²

2015

Somatostatin Analogues

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Heterooligomerization of human dopamine receptor 2 and somatostatin receptor 2

Cited by 116 publications

References 53 publications

Expression of Somatostatin and Dopamine 2 Receptors in Neuroendocrine Tumours and the Potential Role for New Biotherapies

Expression of Somatostatin and Dopamine 2 Receptors in Neuroendocrine Tumours and the Potential Role for New Biotherapies

Somatostatin and dopamine receptor interaction in prostate and lung cancer cell lines

Cortistatins and Dopastatins

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