Expression and characterization of the substance P (NK1) receptor in the rat pituitary and AtT20 mouse pituitary tumor cells

Winkler, Anett; Papsdorf, G; Odarjuk, J.; Siems, Wolf‐Eberhard; Fickel, Jörns; Melzig, Matthias F.

doi:10.1016/0922-4106(95)90188-4

Cited by 14 publications

(11 citation statements)

References 12 publications

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“…To date, three categories of SP-binding neurokinin receptors have been described: NK 1 , with primary affinity for SP; NK 2 , with primary affinity for NKA; and NK 3 , with primary affinity for neurokinin B. NK 1 mRNA encodes a seven-transmembrane domain tachykinin receptor, with preferential affinity to SP [28, 29], and is widely expressed in the central and peripheral nervous system [30]and in the AP [31]. Recently, a highly potent and specific NK 1 receptor antagonist (RPR 100893) has been synthesized [32]and characterized [33, 34, 35, 36, 37].…”

Section: Introductionmentioning

confidence: 99%

Variations in Plasma Levels of Substance P and Effects of a Specific Substance P Antagonist of the NK<sub>1</sub> Receptor on Preovulatory LH and FSH Surges and Progesterone Secretion in the Cycling Cynomolgus Monkey

et al. 2000

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These studies investigated the role of substance P (SP) in the regulation of the hypothalamic-pituitary-ovarian axis in cynomolgus monkeys with normal menstrual cycles. Plasma concentrations of SP were determined in blood samples taken every morning in normally menstruating cynomolgus monkeys throughout the menstrual cycle. There was a significant decreasing linear trend of SP during the follicular phase (cycle day –13 to day 0) and a significant inverse relationship between SP plasma values and plasma 17β-estradiol (E₂) values from day –13 to day 0 of the adjusted cycle. Correspondingly, SP area under the curve was significantly greater during the follicular phase than the luteal phase. In a second experiment, plasma concentrations of E₂, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone and length of cycles were measured after five daily intragastric administrations (10 mg/kg) of an NK₁ receptor (SP receptor) antagonist (RPR 100893; 10 mg/kg) initiated after serum E₂ concentrations had exceeded 125 pg/ml. There was a statistically significant reduction in the amplitude (41% of control) and the area under the curve (37% of control) of the preovulatory LH surge. In addition, there was a reduction of the duration of the LH surge (3 ± 0.1 days in controls vs. 2.1 ± 0.2 days in treated animals). The present results show for the first time that there are significant variations in plasma levels of SP, with a strong negative correlation with serum levels of E₂ during the follicular phase of the cynomolgus monkey, and that endogenous SP has a potentiating role in the interactive hypothalamo-anterior-pituitary mechanisms which lead to the preovulatory LH and FSH surges during the menstrual cycle in the monkey.

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Section: Introductionmentioning

confidence: 99%

Variations in Plasma Levels of Substance P and Effects of a Specific Substance P Antagonist of the NK<sub>1</sub> Receptor on Preovulatory LH and FSH Surges and Progesterone Secretion in the Cycling Cynomolgus Monkey

et al. 2000

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“…NK-1R belongs to the class of seven transmembrane domain receptors that interact with intracellular effector systems via guanine nucleotide-binding regulatory proteins (G-proteins) (Quartara and Maggi, 1997). NK-1R is abundantly present in the rat pituitary and in AtT20 mouse pituitary tumor cells, giving a hint that this receptor might be involved in the pathogenesis of these tumors (Winkler et al, 1995). Furthermore, in human glioma cells, NK-1R stimulated by SP triggers a number of biologic responses that are potentially relevant for tumor growth and progression (Lieb et al, 1997(Lieb et al, , 1998Palma et al, 1999b).…”

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confidence: 99%

Neurokinin-1 Receptor Expression and Its Potential Effects on Tumor Growth in Human Pancreatic Cancer

Frieß

Zhu

Liard

et al. 2003

Laboratory Investigation

106

111

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SUMMARY:The neurokinin-1 receptor (NK-1R) and its ligand substance P (SP) are involved in the pathogenesis of certain neural tumors. Because nerves are significantly altered in pancreatic cancer, evidence for alteration of this pathway in human pancreatic cancer was sought. Expression of NK-1R was analyzed by real-time quantitative RT-PCR, in situ hybridization, immunohistochemistry, and Western blot analysis in normal human pancreatic and pancreatic cancer tissue samples and in pancreatic cancer cell lines. Furthermore, the influence of SP analogs and of the NK-1R antagonist MEN 11467 on pancreatic cancer cell growth was analyzed by sulforhodamine B (SRB) assay. By real-time quantitative RT-PCR, NK-1R mRNA was increased 36.7-fold (p Ͻ 0.001) in human pancreatic cancer samples compared with normal controls. Enhanced NK-1R expression levels were not related to tumor grade but were associated with advanced tumor stage and poorer prognosis. By in situ hybridization and immunohistochemistry, NK-1R mRNA and immunoreactivity were only occasionally weakly present in acinar and ductal cells in the normal pancreas. In contrast, moderate to strong NK-1R mRNA signals and immunoreactivity were present in most cancer cells. By Western blot analysis, NK-1R was increased 26-fold (p Ͻ 0.01) in pancreatic cancer samples in comparison to normal controls. NK-1R mRNA was detected in five pancreatic cancer cell lines by real-time quantitative RT-PCR, with the highest levels in CAPAN-1 cells and the lowest in ASPC-1 cells. SP analogs stimulated pancreatic cancer cell growth, depending on the NK-1R expression level, and this effect could be blocked by a selective NK-1R antagonist. These findings illustrate that the NK-1R pathway is activated in human pancreatic cancer and has the potential to contribute to cancer cell growth, thus suggesting the existence of a neuro-cancer cell interaction in vivo. (Lab Invest 2003, 83:731-742).

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“…Research on neuroimmune-related molecules in breast cancer development is relatively limited when compared with other molecular studies in breast cancer research. Several lines of basic, translational, and clinical research show that neurotrophic factors and neurotransmitters could be involved in tumorigenesis (6)(7)(8)(9). Tac1 is a single copy gene with seven exons that is conserved by evolution (10).…”

Section: Introductionmentioning

confidence: 99%

“…In BCCs, tachykinins interact with neurokinin-1 (NK1) and neurokinin-2 (NK2), both G protein-coupled, seven-transmembrane receptors (11), which leads to autocrine proliferation (5,9). This is not surprising because NK1 and Tac1 peptides are also linked to the development of other cancers (7,(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Factor-κB Is Central to the Expression of Truncated Neurokinin-1 Receptor in Breast Cancer: Implication for Breast Cancer Cell Quiescence within Bone Marrow Stroma

et al. 2007

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Breast cancer is a leading cause of mortality among women in the United States. Tac1 and neurokinin-1 (NK1) are involved in autocrine stimulation of breast cancer cells (BCCs). The single NK1 gene produces full-length (NK1-FL) and truncated (NK1-Tr) forms. NK1-Tr mediates malignancy in breast cells. We now report a critical role for nuclear factor-KB (NF-KB) in the expression of NK1-Tr, but not NK1-FL, in human BCCs. By Western and Northern blot analyses, NK1-FL and NK1-Tr were coexpressed in BCCs but were undetectable in nontumorigenic cells. Loss of repressive activity within the 5 ¶ flanking region of the NK1 partly accounts for constitutive expression of NK1 in BCCs but could not account for the presence of NK1-Tr. Transient transfections with dominant-negative and wildtype IKB show that activation of NF-KB is required for the expression of NK1-Tr. Tac1 gene was linked to the generation of NK1-Tr because its overexpression in BCCs led to the production of multiple cytokines that can activate NF-KB to mediate NK1-Tr expression. Studies with Tac1 knockdown BCCs and Tac1-expressing nontumorigenic breast cells verified a role for NF-KB in the expression of NK1-Tr. The quiescent phenotype of BCCs on contact with bone marrow stroma was partly explained by decreased NF-KB activation and undetectable NK1-Tr. In summary, this study shows a role for NF-KB in the expression of NK1-Tr in BCCs, which seems to be reversed by bone marrow stromal cells. [Cancer Res 2007;67(4):1653-9]

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Expression and characterization of the substance P (NK1) receptor in the rat pituitary and AtT20 mouse pituitary tumor cells

Cited by 14 publications

References 12 publications

Variations in Plasma Levels of Substance P and Effects of a Specific Substance P Antagonist of the NK<sub>1</sub> Receptor on Preovulatory LH and FSH Surges and Progesterone Secretion in the Cycling Cynomolgus Monkey

Variations in Plasma Levels of Substance P and Effects of a Specific Substance P Antagonist of the NK<sub>1</sub> Receptor on Preovulatory LH and FSH Surges and Progesterone Secretion in the Cycling Cynomolgus Monkey

Neurokinin-1 Receptor Expression and Its Potential Effects on Tumor Growth in Human Pancreatic Cancer

Nuclear Factor-κB Is Central to the Expression of Truncated Neurokinin-1 Receptor in Breast Cancer: Implication for Breast Cancer Cell Quiescence within Bone Marrow Stroma

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