The dopamine D2 receptor is expressed in GH3 cells

Johnston, Jennifer; Wood, Diana; Bolaji, E. A.; Johnston, Desmond G.

doi:10.1677/jme.0.0070131

Cited by 14 publications

(15 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding may well account for all of the observed effects of bromocriptine in this study, and is in agreement with the results obtained by Johnston et al [5], who demonstrated that the D 2 R is expressed in GH 3 cells. However, the amount of D 2 Rs per cell was reduced compared with normal controls and they only showed low-affinity binding characteristics [4,5].…”

Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

“…GH 3 cells lack high affinity DA binding sites [4], but they still express D 2 R mRNA as identified by Nothern blot analysis [5]. In addition, the putative D 2 R protein was identified in GH 3 cell membrane preparations subjected to SDS-PAGE analysis [5]. Stimulation of the D 2 R produces a variety of intracellular responses including inhibition of adenylate cyclase (AC) [6][7][8][9], changes in potassium channel activity [10,11], inhibition of transmembrane calcium fluxes [12,13] and a reduction in phosphatidylinositol turnover [9,14].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Distinct Guanine Nucleotide Binding Protein Alpha-Subunit Receptor Coupling in GH Cell Lines: <i>Effects of Bromocriptine and Hormones on Effector Enzyme Modulation</i>

Johansen

Paulssen²,

Bjøro³

et al. 2001

Cell Physiol Biochem

View full text Add to dashboard Cite

The purpose of the present study was to elucidate how the dopamine agonist bromocriptine affected receptor-effector systems in GH cells by measuring adenylate cyclase (AC) and phospholipase C (PL-C) modulation in cell membrane preparations. To perturb the interaction between the receptor and G-protein, polyclonal antibodies reacting with the predicted C-terminal amino acid sequence of G-protein α-subunits were used. The effect of bromocriptine on secretagogue elicited prolactin (PRL) secretion from whole cells was also monitored. Bromocriptine inhibited the basal secretion of PRL in a dose dependent manner, and completely abolished both the thyroliberin (TRH) and the vasoactive intestinal peptide (VIP) stimulated PRL secretion in GH₃ cells. Maximal inhibitory effect on PRL egress elicited by both hormones was obtained at 10-50 µM of bromocriptine. Messenger RNAs for both the short and long form of the D₂ receptor (D₂R) were demonstrated in all three GH cell lines using the RT-PCR technique, advocating that D₂Rs are coupled to distinct G-proteins and, thus, probably being responsible for the observed effects of bromocriptine in these cell lines. Basal AC activity, as measured in membrane preparations of GH₃ cells, remained unaffected by bromocriptine treatment (10 µM), while TRH and VIP stimulated AC activities (175% and 350% of control values, respectively) were partially inhibited (by some 50%). This inhibitory effect of bromocriptine was completely and specifically abolished in the presence of an antiserum against G_i2α. Basal PL-C activity was also unaffected by bromocriptine, while TRH stimulated PL-C activity (350% of control value) was inhibited by bromocriptine (10 µM) by approximately 50%. Immunoblocking of G_q/11α, however, reduced the stimulatory effect of TRH on PL-C activation by some 65%, while an antiserum against G_oα partly counteracted the inhibitory effect of bromocriptine (10 µM) on TRH stimulated PL-C activity. Thus, TRH dependent AC stimulation was counteracted by bromocriptine via G_i2. TRH activation of PL-C occurs via G_q/11, while inhibition by bromocriptine appears to involve G_o. These mechanisms probably account for the major part of the actions of bromocriptine, however, other not yet recognised intermediates may be involved.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct Guanine Nucleotide Binding Protein Alpha-Subunit Receptor Coupling in GH Cell Lines: <i>Effects of Bromocriptine and Hormones on Effector Enzyme Modulation</i>

Johansen

Paulssen²,

Bjøro³

et al. 2001

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Rat ovarian tissue RNA was utilized as a positive control. The GH3 cells expressed SSTRs including all of SSTR1, 2, 3, 4, and 5 and dopamine receptor D2R as reported previously (Johnston et al 1991, Yang et al 2005. The expression level of SSTR2 in GH3 cells was relatively high when compared with that in rat pituitary tissues, while D2R transcript was comparably low in GH3 cells.…”

Section: Resultssupporting

confidence: 78%

Involvement of bone morphogenetic protein-4 in GH regulation by octreotide and bromocriptine in rat pituitary GH3 cells

Miyoshi¹,

Otsuka²,

Otani³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

Here we investigated roles of the pituitary bone morphogenetic protein (BMP) system in modulating GH production regulated by a somatostatin analog, octreotide (OCT) and a dopamine agonist, bromocriptine (BRC) in rat pituitary somatolactotrope tumor GH3 cells. The GH3 cells were found to express BMP ligands, including BMP-4 and BMP-6; BMP type-1 and type-2 receptors (except the type-1 receptor, activin receptor-like kinase (ALK)-6); and Smad signaling molecules. Forskolin stimulated GH production in accordance with cAMP synthesis. BRC, but not OCT, suppressed forskolin-induced cAMP synthesis by GH3 cells. Individual treatment with OCT and BRC reduced forskolininduced GH secretion. A low concentration (0 . 1 mM) of OCT in combination with BRC (1-100 mM) exhibited additive effects on reducing GH and cAMP production induced by forskolin. However, a high concentration (10 mM) of OCT in combination with BRC failed to suppress GH and cAMP production. BMP-4 specifically enhanced GH secretion and cAMP production induced by forskolin in GH3 cells. BRC, but not OCT, inhibited BMP-4-induced activation of Smad1,5,8 phosphorylation and Id-1 transcription and decreased ALK-3 expression. Of note, in the presence of a high concentration of OCT, the BRC effects suppressing BMP-4-Smad1,5,8 signaling were significantly impaired. In the presence of BMP-4, a high concentration of OCT also attenuated the BRC effects suppressing forskolin-induced GH and cAMP production. Collectively, a high concentration of OCT interferes with BRC effects by reducing cAMP production and suppressing BMP-4 signaling in GH3 cells. These findings may explain the mechanism of resistance of GH reduction to a combination therapy with OCT and BRC for GH-producing pituitary adenomas.

show abstract

“…In GH3 cells, D2R expression is not well established [23, 24] and it has been shown that exposing cells to growth factors (i.e. EGF or NGF) induces the expression of functional D2R [25].…”

Section: Resultsmentioning

confidence: 99%

Signaling Pathway Involved in the Pro-Apoptotic Effect of Dopamine in the GH3 Pituitary Cell Line

Jaubert

Ichas²,

Bresson³

2006

Neuroendocrinology

View full text Add to dashboard Cite

Besides its physiological role as a neurotransmitter, dopamine (DA) induces apoptosis in the central nervous system. This effect is mediated partly by the DA transporter (DAT) and involves reactive oxygen species (ROS) formation as well as oxidative stress. In the pituitary, the inhibitory control by DA of prolactin release and synthesis and lactotrope cell proliferation is well known, while the pro-apoptotic effect of DA remains unclear. Our aim was to study the pro-apoptotic effect of DA in the GH3 mammosomatotrope cell line and determine the DA mechanism that leads to apoptosis in these cells. Using flow cytometry, Western blot, and confocal microscopy, we showed for the first time that DA induced: (1) loss of mitochondrial potential; (2) relocation of Bax to the mitochondria; (3) cytochrome c release; (4) caspase-3 activation, and (5) nuclear fragmentation, resulting in apoptosis. We observed that DAT was expressed in GH3 cells and participated in the DA effect, as apoptosis was significantly reversed in the presence of DAT inhibitors. Direct measurement showed that DA rapidly increased the formation of intracellular ROS. The antioxidant N-acetyl-L-cysteine (NAC) effectively blocked DA-induced ROS formation and apoptosis. Neither JNK nor p38 were involved in this process, so we suggest that the mitochondrial pore of transition is the likely target of the ROS generated by DA. These data provide the first evidence that DA triggers apoptosis in pituitary cells via a mechanism involving DAT and oxidative stress. These findings may be particularly relevant in understanding lactotrope apoptosis during postnatal life.

show abstract

The dopamine D2 receptor is expressed in GH3 cells

Cited by 14 publications

References 16 publications

Distinct Guanine Nucleotide Binding Protein Alpha-Subunit Receptor Coupling in GH Cell Lines: <i>Effects of Bromocriptine and Hormones on Effector Enzyme Modulation</i>

Distinct Guanine Nucleotide Binding Protein Alpha-Subunit Receptor Coupling in GH Cell Lines: <i>Effects of Bromocriptine and Hormones on Effector Enzyme Modulation</i>

Involvement of bone morphogenetic protein-4 in GH regulation by octreotide and bromocriptine in rat pituitary GH3 cells

Signaling Pathway Involved in the Pro-Apoptotic Effect of Dopamine in the GH3 Pituitary Cell Line

Contact Info

Product

Resources

About