Neuropeptide Y (NPY) receptors in HEL cells: comparison of binding and functional parameters for full and partial agonists and a non‐peptide antagonist

Feth, Friedhelm; Rascher, Wolfgang; Michel, Martin C.

doi:10.1111/j.1476-5381.1992.tb14212.x

Cited by 33 publications

(15 citation statements)

References 25 publications

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“…Our cross-desensitization experiments with adrenaline and NPY demonstrate that adrenaline induced only homologous desensitization whereas NPY also caused considerable heterologous desensitization of the adrenaline response. This may be related to the fact that NPY is a considerably more effective agonist which may in turn be related to the fact that HEL-cells have only approximately 6,000 a2-adrenoceptors (McKernan et al, 1987) but more than 40,000 NPY receptors per cell (Feth et al, 1992). Homologous desensitization of the M2-adrenoceptor response is not specific for phenylethylamine or imidazoline agonists since adrenaline and moxonidine desensitized each others responses to the same extent as their own.…”

Section: Discussionmentioning

confidence: 99%

“…The free intracellular Ca2+ concentration was determined with the fluorescent inhibitor dye, fura-2, in a Hitachi F2000 spectrofluorometer as previously described (Feth et al, 1992). Briefly, experiments were performed in buffer of the following composition (mM): HEPES 20, NaCl 120, KH2PO4 5, Mg acetate 1, CaCl2 1 and glucose 1 mg ml-' at pH 7.4 using approximately 6-8 x 105 cells ml-'.…”

Section: Ca2+ Measurementsmentioning

confidence: 99%

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Rapid desensitization of adrenaline‐ and neuropeptide Y‐stimulated Ca²⁺ mobilization in HEL‐cells

Michel

1994

British J Pharmacology

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1 Desensitization of G,-coupled receptors, the P2-adrenoceptor for example, involves rapid and slower components but little is known regarding the existence of rapid desensitization of Gi-coupled 2 Following stimulation by adrenaline or neuropeptide Y Ca2+ levels returned towards baseline a few minutes after agonist addition and were refractory to a second agonist exposure demonstrating rapid desensitization. Cross-desensitization experiments with neuropeptide Y, adrenaline and moxonidine demonstrated the presence of homologous (both receptors) and heterologous desensitization (neuropeptide Y receptors only), and that the x2A-adrenoceptor desensitization was not specific for phenylethylamine (adrenaline) or imidazoline agonists (moxonidine). 3 The protein kinase C activator, phorbol ester, rapidly desensitized the hormonal Ca2+ responses and inhibitors of protein kinase C enhanced the hormonal responses inconsistently. The tyrosine kinase inhibitor, herbimycin, enhanced Ca2+ mobilization by adrenaline and neuropeptide Y, whereas the protein phosphatase inhibitor, okdadaic acid, did not affect Ca2+ mobilization or its desensitization. 4 In the absence of extracellular Ca2+ the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, reduced hormone-stimulated Ca2+ elevations, demonstrating that mobilization occurs from a thapsigargin-sensitive pool in the endoplasmic reticulum. The inositol phosphate-independent Ca2' release modulator, ryanodine, significantly enhanced adrenaline-and neuropeptide Y-stimulated Ca2+ elevations. Blockade of the endoplasmic reticulum Ca2+-ATPase by thapsigargin in the presence of extracellular Ca2+ enhanced hormone-stimulated Ca2+ increases, demonstrating the importance of this enzyme for the termination of the Ca2+ signal. 5 It is concluded that adrenaline and neuropeptide Y-stimulated Ca2+ mobilization in HEL-cells occurs from a thapsigargin-and ryanodine-sensitive store in the endoplasmic reticulum and desensitizes rapidly; this appears to involve multiple mechanisms including protein kinases, possibly acting on receptors, and Ca2+ release and sequestration mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Ca2+ Measurementsmentioning

confidence: 99%

Rapid desensitization of adrenaline‐ and neuropeptide Y‐stimulated Ca²⁺ mobilization in HEL‐cells

Michel

1994

British J Pharmacology

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“…1A) revealed that the affinity (K d ) of the receptor is in the physiologic range (27). Earlier studies have shown that SK-N-MC (7, 27) HEL cells (28) and several other neuroblastoma cell lines express high-affinity NPY receptors in the nanomolar range (29). Our present studies showed that NPY receptor subtype-specific peptide ligands inhibited 125 I-PYY binding to MCF-7 membranes in a dose-dependent manner (Fig.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Up-regulates Neuropeptide Y Y1 Receptor Expression in a Human Breast Cancer Cell Line

Amlal¹,

Faroqui²,

Balasubramaniam

et al. 2006

Cancer Research

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Normal breast tissue mainly expresses the neuropeptide Y (NPY) Y2 receptor whereas primary human breast carcinomas express the Y1 receptor (Y1R) subtype. We hypothesized that activation of estrogen signaling systems plays a role in the induction of Y1R. To investigate this possibility, we used estrogen receptor-positive (ER+) human breast carcinoma cell line, MCF-7, and examined the effect of estrogen on Y1R gene expression and its signaling pathways. Saturation binding studies revealed that MCF-7 cells express high-affinity NPY receptor. NPY inhibited forskolin-stimulated adenosine 3V 5V -cyclic monophosphate (cAMP) accumulation and mobilized intracellular Ca 2+ in MCF-7 cells. Chronic estrogen treatment enhanced NPY-mediated inhibition of cAMP accumulation by 4-fold and caused a significant increase in Y1R mRNA expression through ERA. Similarly, estrogen increased Y1R mRNA expression in T-47D (ER+) but not in MDA-MB231 or MDA-MB468 (ERÀ) cell lines. Cycloheximide decreased basal Y1R mRNA expression; however, it did not affect its increase by estrogen. Moreover, estrogen treatment of MCF-7 cells did not increase Y1R mRNA stability. The up-regulation of Y1R expression by estrogen is prevented by hydroxyurea but not by nocodazole or IB-MECA (cell cycle inhibitors). Lastly, NPY inhibited estrogen-induced cell proliferation through Y1R. In conclusion, MCF-7 cells express a functional Y1R coupled to both Ca 2+ and cAMP pathways. Estrogen up-regulates Y1R expression through ERA. This effect is independent of increased Y1R mRNA stability or new protein synthesis, and likely occurs during S phase completion of the cell cycle. Estrogen plays an important role in the up-regulation of Y1R, which in turn regulates estrogen-induced cell proliferation in breast cancer cells. (Cancer Res 2006; 66(7): 3706-14)

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“…The nature of the transmitter(s) released from the PC12 cells is uncertain at present since the sensor cells chosen may react to many transmitter substances, e.g. at least to noradrenaline and NPY [10,12,24,25]. However, the result obtained using the α 2 -adrenoceptor antagonist RX821002 suggests that the catecholamines, most likely noradrenaline, are partially responsible for the HEL cell signal.…”

Section: Discussionmentioning

confidence: 87%

“…HEL 92.1.7 human erythroleukemia cells, which show robust [Ca 2+ ] i responses to many neurotransmitters such as catecholamines and neuropeptide Y (NPY) [10,11,12,24,25] but not to depolarisation, were chosen as the target/sensor model. We have also investigated the pharmacology of VGCC and their relationship with transmitter release.…”

Section: Introductionmentioning

confidence: 99%

Reconstitution of neurotransmission by determining communication between differentiated PC12 pheochromocytoma and HEL 92.1.7 erythroleukemia cells

Shariatmadari

Lund

Krijukova

et al. 2001

Pfl�gers Archiv European Journal of Physiology

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Neurotransmitter release was monitored using fura-2-loaded HEL 92.1.7 cells dispersed among differentiated PC12 cells (loaded with another Ca2+ indicator fluo-3) and immobilised using transparent polycarbonate membrane filters with uniform pore size. Depolarisation with K+ caused a rapid rise in Ca2+ concentration in the PC12 cells, followed by a delayed secondary Ca2+ response in simultaneously monitored nearby HEL cells. There was a lag period of about 20 s between the responses of the two cell types. Voltage-gated Ca2+ channels in PC12 cells were inhibited by the P/Q-type (omega-conotoxin MVIIC, omega-agatoxin IVA), N-type (omega-conotoxin GVIA) and L-type channel blockers (nifedipine) as determined using fura-2 or whole-cell patch-clamp recordings. The communication between the cell types on the other hand was sensitive to P/Q- and N-type but not to L-type channel blockers. This suggests that, as in neurons, P/Q- and N-type Ca2+ channels mediate the release of neurotransmitters acting on HEL cells. Theoretically, the procedure employed should be sensitive enough to detect single exocytotic events. Our results demonstrate that a random distribution between effector and target cells is sufficient to allow communication between cells in a manner similar to extrasynaptic transmission.

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Neuropeptide Y (NPY) receptors in HEL cells: comparison of binding and functional parameters for full and partial agonists and a non‐peptide antagonist

Cited by 33 publications

References 25 publications

Rapid desensitization of adrenaline‐ and neuropeptide Y‐stimulated Ca²⁺ mobilization in HEL‐cells

Rapid desensitization of adrenaline‐ and neuropeptide Y‐stimulated Ca²⁺ mobilization in HEL‐cells

Estrogen Up-regulates Neuropeptide Y Y1 Receptor Expression in a Human Breast Cancer Cell Line

Reconstitution of neurotransmission by determining communication between differentiated PC12 pheochromocytoma and HEL 92.1.7 erythroleukemia cells

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Neuropeptide Y (NPY) receptors in HEL cells: comparison of binding and functional parameters for full and partial agonists and a non‐peptide antagonist

Cited by 33 publications

References 25 publications

Rapid desensitization of adrenaline‐ and neuropeptide Y‐stimulated Ca2+ mobilization in HEL‐cells

Rapid desensitization of adrenaline‐ and neuropeptide Y‐stimulated Ca2+ mobilization in HEL‐cells

Estrogen Up-regulates Neuropeptide Y Y1 Receptor Expression in a Human Breast Cancer Cell Line

Reconstitution of neurotransmission by determining communication between differentiated PC12 pheochromocytoma and HEL 92.1.7 erythroleukemia cells

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Rapid desensitization of adrenaline‐ and neuropeptide Y‐stimulated Ca²⁺ mobilization in HEL‐cells

Rapid desensitization of adrenaline‐ and neuropeptide Y‐stimulated Ca²⁺ mobilization in HEL‐cells