Retinoic acid-induced differentiation of a human neuroblastoma cell line alters muscaric receptor expression

Baumgartner, Melissa K.; Wei, Jian Wen; Aronstam, Robert S.

doi:10.1016/0165-3806(93)90197-i

Cited by 19 publications

(11 citation statements)

References 15 publications

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“…Muscarinic and other hormone and neurotransmitter receptor expression is regulated during in vitro neuronal differentiation. For instance, RA induction of neuroblastoma cells to neuronal differentiation results in an increase of muscarinic receptor expression (56). We have shown that the M3 receptor gene expression increases during the course of neuronal differentiation (Fig.…”

Section: Inhibition Of Formation Of Ebs In the Presence Of The B2bkr mentioning

confidence: 87%

Neuronal Differentiation of P19 Embryonal Carcinoma Cells Modulates Kinin B2 Receptor Gene Expression and Function

Martins

Resende

Majumder

et al. 2005

Journal of Biological Chemistry

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Kinins are vasoactive oligopeptides generated upon proteolytic cleavage of low and high molecular weight kininogens by kallikreins. These peptides have a well established signaling role in inflammation and homeostasis. Nevertheless, emerging evidence suggests that bradykinin and other kinins are stored in the central nervous system and may act as neuromediators in the control of nociceptive response. Here we show that the kinin-B2 receptor (B2BKR) is differentially expressed during in vitro neuronal differentiation of P19 cells. Bradykinin (BK)1 and kallidin are biological active peptides generated by the proteolytic cleavage of kininogens by serine proteases of the kallikrein family. High molecular weight kininogens are precursors of BK, whereas low molecular weight kininogens give origin to kallidin. Along with other kinins, BK and kallidin elicit a wide range of physiological responses, being classically involved in the control of cardiovascular homeostasis and inflammation. As a matter of fact, altered function of the kallikrein-kinin system has been implicated in the development of various pathological conditions such as arthritis, pancreatitis, and asthma (for a review see Refs. 1 and 2). Emerging evidence shows that kinins are stored in neuronal cells of the central nervous system and may act as neuromediators in various functions, including the control of nociceptive information (for a review see Ref.3). Expression of kallikrein in developing rat brains (4) supports the notion that kinin-induced receptor activity might be required during neuronal development. BK has also been shown to enhance the release of neurotransmitters such as noradrenalin and neuropeptide Y by sympathetic neurons, chromaffin cells, and pheochromocytoma cells (5-8). Moreover, BK implication in the control of calcium homeostasis has already been demonstrated in adult sensory neurons (9).Most of the biological actions of BK and kallidin are mediated by a serpentine receptor coupled to a G-protein, the kinin-B2 receptor (B2BKR), which is constitutively expressed and widely distributed throughout central and peripheral tissues under physiological conditions. However, there is evidence that expression of B2BKRs during development is regulated. For instance, B2BKR expression has been shown to be involved in the development of the urinary and cardiovascular systems (10). Inhibition of B2BKR activity in rat embryos resulted in animals with disturbed kidney development (11). Besides being regulated during the ontogenesis of cardiovascular and urinary systems, a large set of evidence exists showing that modulation of B2 receptor expression and function also appears during neuronal development. Thus, it has been detected in central and peripheral noradrenergic neurons, in the spinal cord, in neuronal differentiating PC12 pheochromocytoma cells, and in neuroblastoma and glia-derived cell lines (12-18). A cross-talk between the B2BKR and other hormone and neurotransmitter

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Section: Inhibition Of Formation Of Ebs In the Presence Of The B2bkr mentioning

confidence: 87%

Neuronal Differentiation of P19 Embryonal Carcinoma Cells Modulates Kinin B2 Receptor Gene Expression and Function

Martins

Resende

Majumder

et al. 2005

Journal of Biological Chemistry

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“…mAchRs exist as five molecularly distinct subtypes (M1-M5) with M1 and M3 as the predominant isoforms [5,6,7]. These receptors interact with distinct G protein subunits to signal various cellular functions through specific downstream effector proteins.…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between VEGFR2 and muscarinic receptors regulates the mTOR pathway in serum starved SK-N-SH human neuroblastoma cells

Edelstein¹,

Hao²,

Cao³

et al. 2011

Cellular Signalling

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Muscarinic acetylcholine receptors (mAchRs) are guanosine nucleotide-binding protein (G protein) coupled receptors that crosstalk with receptor tyrosine kinases (RTKs) to signal mitogenic pathways. In particular, mAchRs are known to couple with RTKs for several growth factors to activate the mammalian target of rapamycin (mTOR)/Akt pathway, a regulator of protein synthesis. The RTK for the vascular endothelial growth factor (VEGF), VEGFR2, can signal protein synthesis but whether it cooperates with mAchRs to mediate mTOR activation has not been demonstrated. Using serum starved SK-N-SH neuroblastoma cells, we show that the muscarinic receptor agonists carbachol and pilocarpine enhance the activation of mTOR substrates p70 S6 Kinase (S6K) and its target ribosomal protein S6 (S6) in a VEGFR2 dependent manner. Treatments with carbachol increased VEGFR2 phosphorylation, suggesting that mAchRs stimulate VEGFR2 transactivation to enhance mTOR signaling. Inhibitor studies revealed that phosphoinositide 3 kinase resides upstream from S6K, S6 and Akt phosphorylation while protein kinase C (PKC) functions in an opposing fashion by positively regulating S6K and S6 phosphorylation and suppressing Akt activation. Treatments with the phosphatase inhibitors sodium orthovanadate and okadaic acid increase S6, Akt and to a lesser extent S6K phosphorylation, indicating that tyrosine and serine/threonine dephosphorylation also regulates their activity. However, okadaic acid elicited a far greater increase in phosphorylation, implicating phosphatase 2A as a critical determinant of their function. Finally, pilocarpine but not carbachol induced a time and dose dependent cell death that was associated with caspase activation and oxidative stress but independent of S6K and S6 activation through VEGFR2. Accordingly, our findings suggest that mAchRs crosstalk with VEGFR2 to enhance mTOR activity but signal divergent effects on survival through alternate mechanisms.

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“…Similar cholinergic features are acquired by neuroblastoma cells differentiated with retinoic acid (Handler et al, 2000). Neuroblastoma cells have also been shown to express functional muscarinic receptors of acetylcholine (M 1 -M 5 ) (Baumgartner et al, 1993). Stimulation of serum-starved neuroblastoma cells with a non-specific muscarinic agonist, carbochol, resulted in an increase in their survival.…”

Section: Neuropeptide Y -Neuronal Marker or Growth Factor?mentioning

confidence: 72%

“…They are also known to express their receptors, which creates functional autocrine loops (Baumgartner et al, 1993;Bawa-Khalfe et al, 2007;Kitlinska et al, 2005;Parsley et al, 1999). Sympathetic neurotransmitters, in turn, are known to be potent regulators of many processes involved in the regulation of tumor growth, such as cell proliferation, survival, migration and angiogenesis (Greenwood & Dragunow, 2010;Kitlinska et al, 2005;Laifenfeld et al, 2002;Lee et al, 2003b;Yaniv et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Sympathetic Neurotransmitters in Neuroblastoma – Between Physiology and Pathology

Czarnecka¹,

Tilan²,

Kitlińska³

2012

Neuroblastoma - Present and Future

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Retinoic acid-induced differentiation of a human neuroblastoma cell line alters muscaric receptor expression

Cited by 19 publications

References 15 publications

Neuronal Differentiation of P19 Embryonal Carcinoma Cells Modulates Kinin B2 Receptor Gene Expression and Function

Neuronal Differentiation of P19 Embryonal Carcinoma Cells Modulates Kinin B2 Receptor Gene Expression and Function

Crosstalk between VEGFR2 and muscarinic receptors regulates the mTOR pathway in serum starved SK-N-SH human neuroblastoma cells

Sympathetic Neurotransmitters in Neuroblastoma – Between Physiology and Pathology

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