Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The D2 dopamine receptor isoforms signal to a variety of cellular effectors in both the central nervous system and periphery. Two alternative splice forms of the D2 dopamine receptor exist, the D2s (short) and D2l (long), which has an insertion of 29 amino acids in the third intracellular loop (). In cells of the anterior lobe of the pituitary, D2 dopamine receptors (both forms) are present on lactotroph cells coupled to the inhibition of adenylyl cyclase, activation of voltage-gated calcium channels, and inhibition of potassium channels. We describe here a novel signaling pathway for the D2s, which is the activation of phospholipase D (PLD). GH4C1 cells, a clonal line derived from a rat pituitary tumor, were stably transfected with the gene encoding the D2s, generating GH4-121 cells. Treatment of GH4-121 cells with a dopaminergic agonist resulted in activation of PLD in both a dose-dependent and time-dependent manner. This signaling pathway was not inhibited by prior treatment of cells with pertussis toxin at concentrations that ablate other D2s receptor signaling in this cell line. The stimulation of PLD activity by D2s appeared to correlate with the presence of a specific protein kinase C isoform, PKCepsilon. The D2s stimulation of PLD activity was blocked by preincubation of cells with C3 exoenzyme, indicating that the stimulation of PLD may involve Rho family members. The stimulation of PLD by dopaminergic agonists took place in the absence of any detectable stimulation of phosphoinositide metabolism.
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PMID:The D2s dopamine receptor stimulates phospholipase D activity: a novel signaling pathway for dopamine. 1090 15

Regulation of the PI3K-protein kinase B/Akt (serine/threonine kinase) cascade by PRL-releasing peptide (PrRP) and insulin in GH3 rat pituitary tumor cells was investigated. PrRP and insulin rapidly and transiently stimulated the activation of Akt, and the PI3K inhibitor wortmannin blocked the PrRP- or insulin-induced activation of Akt. Both pertussis toxin (10 ng/ml), which inactivates Gi/Go proteins, and expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase I, which specifically blocks signaling mediated by the betagamma subunits of G proteins, completely blocked the PrRP-induced Akt activation, suggesting that Gi/Go proteins are involved in PrRP-induced Akt activation, as they are in the activation of ERK by PrRP. Moreover, to determine whether a PI3K-Akt cascade regulates rat PRL (rPRL) promoter activity, we transfected the intact rPRL promoter ligated to the firefly luciferase reporter gene into GH3 cells. PrRP and insulin activated the rPRL promoter activity. Pretreatment with wortmannin or cotransfection with a dominant-negative Akt partially but significantly inhibited the induction of the rPRL promoter by PrRP or insulin. Cotransfection with a constitutively active Akt induced the rPRL promoter activity and cotransfection with a dominant-negative cAMP response element-binding protein (CREB) completely abolished the response of the rPRL promoter to the constitutively active Akt. Furthermore, either treatment with PrRP and insulin or transfection with the constitutively active Akt induced the phosphorylation of CREB. These results suggest that PrRP and insulin activate a PI3K-Akt cascade that is necessary to elicit rPRL promoter activity via a CREB-dependent mechanism.
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PMID:Regulation of the PRL promoter by Akt through cAMP response element binding protein. 1175 85

Rat pituitary tumor cells (GC cells) exhibit spontaneous oscillations of intracellular free calcium concentration ([Ca(2+)](i)) that allow continuous release of growth hormone (GH). Of the somatostatin (SRIH) receptor subtypes (sst receptors) mediating SRIH action, sst(1) and sst(2) receptors are highly expressed by GC cell membranes. In the present study, the effects of sst(1) or sst(2) receptor activation on single-cell [Ca(2+)](i) were investigated in GC cells by confocal fluorescence microscopy. In addition, the effects of sst(1) or sst(2) receptor activation on GH secretion were also studied. Our results demonstrate that SRIH decreases [Ca(2+)](i) baseline and almost completely blocks Ca(2+) transients through activation of sst(2) but not of sst(1) receptors. In contrast, SRIH effectively inhibits GH secretion through activation of both sst(1) and sst(2) receptors. Blocking Ca(2+) transients is less efficient than SRIH to inhibit GH release. The cyclic octapeptide, CYN-154806, antagonizes sst(2) receptors at [Ca(2+)](i) since it abolishes the sst(2) receptor-mediated inhibition of [Ca(2+)](i) without affecting single-cell Ca(2+) signals. On the other hand, CYN-154806 alone potently inhibits GH secretion through the involvement of pertussis toxin-sensitive G proteins. In conclusion, the present results demonstrate that SRIH inhibition of GH release in GC cells involves mechanisms either dependent or independent on SRIH modulation of [Ca(2+)](i). The implications of CYN-154806 inhibition of GH secretion are discussed.
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PMID:Inhibitory control of growth hormone secretion by somatostatin in rat pituitary GC cells: sst(2) but not sst(1) receptors are coupled to inhibition of single-cell intracellular free calcium concentrations. 1216 71

Somatostatin limits cell growth by inhibiting the proliferative activity of growth factor receptors. In this study, it is shown that in pituitary tumor cells, the somatostatin analogue octreotide produces its antiproliferative action by inducing the expression the tumor suppressor gene Zac1. ZAC/Zac1 induces cell cycle arrest and apoptosis and is highly expressed in normal pituitary, mammary, and ovarian glands but is down-regulated in pituitary, breast, and ovarian tumors. Knocking down Zac1 by RNA interference abolished the antiproliferative effect of octreotide in pituitary tumor cells, indicating that Zac1 is necessary for the action of octreotide. The effect of octreotide on Zac1 expression was pertussis toxin sensitive and was abolished after transfection with a dominant negative vector for SHP-1. Zac1 is a target of the phosphatidylinositol 3-kinase (PI3K) survival pathway. Octreotide treatment decreased the tyrosine phosphorylation levels of the PI3K regulatory subunit p85, induced dephosphorylation of phosphoinositide-dependent kinase 1 (PDK1) and Akt, and activated glycogen synthase kinase 3beta (GSKbeta). Therefore, in pituitary tumor cells, somatostatin analogues produce their antiproliferative action by acting on the PI3K/Akt signaling pathway and increasing Zac1 gene expression.
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PMID:Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression. 1645 15

Estrogen (E2) has been shown to regulate various functions for many pituitary hormones. Recently, the potential roles of non-genomic pathways in E2-induced actions have been proposed in the previous studies, however, the effects of E2 remain to be elucidated in regard to non-genomic induction of cytosolic protein calbindin-D9k (CaBP-9k). To gain a better understanding of the molecular events underlying E2-induced expression of CaBP-9k, rat pituitary tumor cells (GH3 cells) were treated with E-BSA (membrane impermeable E2-conjugated with BSA). Non-genomic induction of CaBP-9k by E-BSA was determined using RT-PCR and western blot analysis. The significant increase in CaBP-9k mRNA level was observed as early as 15 min following treatment with a high concentration of E-BSA (10(-6)M), whereas rapid and significant induction of CaBP-9k protein was noted at 5, 15 and 30 min after E-BSA exposure (p<0.05). In order to determine the potential involvement of different signaling pathways, several inhibitors were employed, i.e., ICI 182,780 for the estrogen receptor (ER) pathway, pertussis toxin (PTX) for the G-protein-coupled signaling pathway, U0126 (U) for the ERK (extracellular regulated kinase) and wortmannin (W) for the Akt (protein kinase B). Co-treatment with ICI 182, 780 and PTX reversed an E-BSA-induced increase in CaBP-9k mRNA and protein. Although neither U nor W alone attenuated E-BSA-induced effects, these inhibitors together abolished E-BSA-induced CaBP-9k expression, suggesting their involvement in its regulation. Taken together, these results demonstrate the involvement of various signaling pathways in E2-induced regulation of CaBP-9k. In addition, ER and G-protein-coupled signaling pathways may play central roles in the non-genomic activities of E2 and that downstream signaling via ERK and Akt are required to evoke ER-mediated induction of CaBP-9k in vitro.
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PMID:Membrane-impermeable estrogen is involved in regulation of calbindin-D9k expression via non-genomic pathways in a rat pituitary cell line, GH3 cells. 2014 59


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