UMLS:C0043167 - FACTA Search

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of the mitogen-activated protein kinase (MAPK) family by prolactin-releasing peptide (PrRP) in both GH3 rat pituitary tumor cells and primary cultures of rat anterior pituitary cells was investigated. PrRP rapidly and transiently activated extracellular signal-regulated protein kinase (ERK) in both types of cells. Both pertussis toxin, which inactivates G(i)/G(o) proteins, and exogenous 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 ERK activation, suggesting the involvement of G(i)/G(o) proteins in the PrRP-induced ERK activation. Down-regulation of cellular protein kinase C did not significantly inhibit the PrRP-induced ERK activation, suggesting that a protein kinase C-independent pathway is mainly involved. PrRP-induced ERK activation was not dependent on either extracellular Ca(2+) or intracellular Ca(2+). However, the ERK cascade was not the only route by which PrRP communicated with the nucleus. JNK was also shown to be significantly activated in response to PrRP. JNK activation in response to PrRP was slower than ERK activation. Moreover, to determine whether a MAPK family cascade regulates rat prolactin (rPRL) promoter activity, we transfected the intact rPRL promoter ligated to the firefly luciferase reporter gene into GH3 cells. PrRP activated the rPRL promoter activity in a time-dependent manner. Co-transfection with a catalytically inactive form of a MAPK construct or a dominant negative JNK, partially but significantly inhibited the induction of the rPRL promoter by PrRP. Furthermore, co-transfection with a dominant negative Ets completely abolished the response of the rPRL promoter to PrRP. These results suggest that PrRP differentially activates ERK and JNK, and both cascades are necessary to elicit rPRL promoter activity in an Ets-dependent mechanism.
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PMID:Prolactin-releasing peptide activation of the prolactin promoter is differentially mediated by extracellular signal-regulated protein kinase and c-Jun N-terminal protein kinase. 1065 64

Using in situ hybridization and immunoblot analysis, the present studies identified G(z) mRNA and G(z)-protein in the hypothalamic paraventricular nucleus. The role of G(z)-proteins in hypothalamic 5-HT(1A) receptor signaling was examined in vivo. Activation of 5-HT(1A) receptors increases the secretion of oxytocin and ACTH, but not prolactin. Intracerebroventricular infusion (3-4 d) of G(z) antisense oligodeoxynucleotides, with different sequences and different phosphorothioate modification patterns, reduced the levels of G(z)-protein in the hypothalamic paraventricular nucleus, whereas missense oligodeoxynucleotides had no effect. Neither antisense nor missense oligodeoxynucleotide treatment altered basal plasma levels of ACTH, oxytocin, or prolactin, when compared with untreated controls. An antisense-induced decrease in hypothalamic G(z)-protein levels was paralleled by a significant decrease in the oxytocin and ACTH responses to the 5-HT(1A) agonist 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT). In contrast, the prolactin response to 8-OH-DPAT (which cannot be blocked by 5-HT(1A) antagonists) was not inhibited by G(z) antisense oligodeoxynucleotides. G(z)-proteins are the only members of the G(i)/G(o)-protein family that are not inactivated by pertussis toxin. In a control experiment, pertussis toxin treatment (1 microgram/5 microliter, i.c.v.; 48 hr before the 8-OH-DPAT challenge) did not inhibit the ACTH response, potentiated the oxytocin response, and eliminated the prolactin response to 8-OH-DPAT. Thus, pertussis toxin-sensitive G(i)/G(o)-proteins do not mediate the 5-HT(1A) receptor-mediated increase in ACTH and oxytocin secretion. Combined, these studies provide the first in vivo evidence for a key role of G(z)-proteins in coupling hypothalamic 5-HT(1A) receptors to effector mechanisms.
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PMID:Evidence that G(z)-proteins couple to hypothalamic 5-HT(1A) receptors in vivo. 1077 73

The hypocretin/orexins (Hcrts/ORXs) are peptides produced in neurons in the lateral hypothalamic area that project to neuroendocrine centers in the hypothalamus. Hcrt/ORX receptors are present in the hypothalamus and anterior pituitary gland. We examined the possibility that the Hcrts/ORXs, which we have demonstrated previously to act in the brain to stimulate sympathetic function, could alter stress hormone secretion by a direct pituitary action. In vitro studies revealed a dose-related inhibitory effect of the Hcrts/ORXs on corticotropin-releasing hormone-stimulated ACTH secretion that appeared to be mediated via the orexin-1 receptor and to be expressed at doses (threshold dose 1 nM orexin A) similar to the affinity constant for the receptor. The effect was not due to abrogation of the cAMP response of the corticotroph to corticotropin-releasing hormone and was not pertussis toxin sensitive, suggesting a non-G(i)-mediated mechanism. Instead, a G(q)-mediated signaling mechanism was indicated by the ability of protein kinase C blockade with calphostin C to reverse the inhibitory action of orexin A. Orexin A and orexin B did not significantly alter basal ACTH secretion in vitro and did not alter basal or releasing factor-stimulated secretion of luteinizing hormone, prolactin, thyroid-stimulating hormone or growth hormone from cells harvested from male or random-cycle female donors. Our data suggest a direct, pituitary action of the Hcrts/ORXs to modulate the endocrine response to stress and identify the potential cellular mechanism of a unique biological action of the peptides in the anterior pituitary gland.
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PMID:Hypocretin/orexin suppresses corticotroph responsiveness in vitro. 1155 21

In pituitary lactotrophs the prolactin gene is stimulated by neuropeptides and estrogen and is suppressed by dopamine via D2-type receptors. Stimulatory signals converge on activation of the mitogen-activated protein kinases ERK1/2, but dopamine regulation of this pathway is not well defined. Paradoxically, D2 agonists activate ERK1/2 in many cell types. Here we show that in prolactin-secreting GH4ZR7 cells and primary pituitary cells, dopamine treatment leads to a rapid, pronounced, and specific decrease in activated ERK1/2. The response is blocked by D2-specific antagonists and pertussis toxin. Interestingly, in stable lines expressing specific pertussis toxin-resistant Galpha subunits, toxin treatment blocks dopamine suppression of MAPK in Galpha(i2)- but not Galphao-expressing cells, demonstrating that G(o)-dependent pathways can effect the inhibitory MAPK response. At the nuclear level, the MEK1 inhibitor U0126 mimics the D2-agonist bromocryptine in suppressing levels of endogenous prolactin transcripts. Moreover, a good correlation is seen between the IC(50) values for inhibition of MEK1 and suppression of prolactin promoter function (PD184352 > U0126 > U0125). Both dopamine and U0126 enhance the nuclear localization of ERF, a MAPK-sensitive ETS repressor that inhibits prolactin promoter activity. In addition, U0126 suppression is transferred by tandem copies of the Pit-1-binding site, consistent with mapping experiments for dopamine responsiveness. Our data suggest that ERK1/2 suppression is an obligatory step in the dopaminergic control of prolactin gene transcription and that bidirectional control of ERK1/2 function in the pituitary may provide a key mechanism for endocrine gene control.
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PMID:Activation of Go-coupled dopamine D2 receptors inhibits ERK1/ERK2 in pituitary cells. A key step in the transcriptional suppression of the prolactin gene. 1212 79

Dopamine is the primary inhibitory regulator of lactotroph proliferation and prolactin (PRL) secretion in vivo, acting via dopamine D2 receptors (short D2S and long D2L forms). In GH4C1 pituitary cells transfected with D2S or D2L receptor cDNA, dopamine inhibits PRL secretion and DNA synthesis. These actions were blocked by pertussis toxin, implicating G(i)/G(o) proteins. To address roles of specific G(i)/G(o)4 proteins in these actions a series of GH4C1 cell lines specifically depleted of individual Galpha subunits was examined. D2S-mediated inhibition of BayK8644-stimulated PRL secretion was primarily dependent on G(o) over G(i), as observed for BayK8644-induced calcium influx. By contrast, inhibitory coupling of the D2S receptor to TRH-induced PRL secretion was partially impaired by depletion of any single G protein, but especially G(i)3. Inhibitory coupling of D2L receptors to PRL secretion required G(o), but not G(i)2, muscarinic receptor coupling was resistant to depletion of any G(i)/G(o) protein, whereas the 5-HT1A and somatostatin receptors required G(i)2 or G(i)3 for coupling. The various receptors also demonstrated distinct G protein requirements for inhibition of DNA synthesis: depletion of any G(i)/G(o) subunit completely uncoupled the D2S receptor, the D2L receptor was uncoupled by depletion of G(i)2, and muscarinic and somatostatin receptors were resistant to depletion of G(i)2 only. These results demonstrate distinct receptor-G protein preferences for inhibition of TRH-induced PRL secretion and DNA synthesis.
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PMID:G protein preferences for dopamine D2 inhibition of prolactin secretion and DNA synthesis in GH4 pituitary cells. 1214 43

Two Ca(2+)-mobilizing receptors expressed in lactotrophs, endothelin-A (ET(A)) and thyrotropin-releasing hormone (TRH), induce a rapid Ca(2+) release from intracellular stores and prolactin (PRL) secretion but differ in their actions during the sustained stimulation; TRH facilitates and ET-1 inhibits voltage-gated calcium influx (VGCI) and PRL secretion. In pertussis toxin (PTX) treated cells, ET-1-induced inhibition of VGCI was abolished and the pattern of Ca(2+) signaling was highly comparable with that observed in TRH-stimulated cells. The addition of Cs(+), a relatively specific blocker of inward rectifier K(+) channels, mimicked the effect of PTX on the pattern of ET-1-induced sustained Ca(2+) signaling, but only in about 50% of cells, and did not affect agonist-induced inhibition of PRL secretion. Extracellular Cs(+) was also ineffective in altering the TRH-induced facilitation of VGCI and PRL secretion. Furthermore, apamin and paxilline, specific blockers of Ca(2+)-activated SKand BK-type K(+) channels, respectively; E-4031, a blocker of ether a-go-go K(+) channel; and linopirdine, a blocker of M-type K(+) channel, did not affect the agonist-specific patterns of calcium signaling and PRL secretion. These results suggest that ET-1 inhibits VGCI through activation of Cs(+)-sensitive channels, presumably the Gi/o-controlled inward rectifier K(+) channels, and that this agonist also inhibits PRL release, but downstream of Ca(2+) influx. Further studies are required to identify the mechanism of sustained TRH-induced facilitation of VGCI and PRL secretion.
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PMID:Dependence of prolactin release on coupling between Ca(2+) mobilization and voltage-gated Ca(2+) influx pathways in rat lactotrophs. 1266 67

Two-way communication exists between the endocrine and immune systems using molecules such as hormones and cytokines. Here we describe a new pathway by which C3a, a complement-derived cytokine, stimulates anterior pituitary hormone release and activates the hypothalamic-pituitary-adrenal axis, a reflex central to the stress response and to the control of inflammation. We show that C3a receptors are expressed in pituitary hormone secreting and non-hormone secreting (folliculostellate) cells and that both C3a and C3adesArg (a non-inflammatory metabolite) stimulate pituitary cell cultures to release prolactin, growth hormone, and adrenocorticotropin. Serum levels of these hormones, together with adrenal corticosterone, increase dose dependently with recombinant C3a and C3adesArg administration in vivo. Pertussis toxin blocks the response to C3a but not C3adesArg, which indicates the presence of two receptors, only one of which is coupled to Galphai-proteins. We propose that the complement innate immune molecules (cytokines) modulate tissue-specific and systemic inflammatory responses through communication with the endocrine pituitary gland.
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PMID:Complement C3a receptors in the pituitary gland: a novel pathway by which an innate immune molecule releases hormones involved in the control of inflammation. 1456 92

Attachment of leukocytes to endothelial cells is an essential step for the extravasation and recruitment of cells at sites of inflammation. The pituitary hormone prolactin (PRL) is involved in the inflammatory process. Here, we show that treatment with PRL of human peripheral blood mononuclear cells (PBMC) stimulates their adhesion to human umbilical vein endothelial cells (HUVEC) activated by interleukin-1beta. Stimulation of adhesion by PRL is mediated via integrins leukocyte functional antigen-1 (LFA-1) and very late antigen-4 (VLA-4), because immunoneutralization of both integrins prevents PRL action. Also, PRL promotes the adhesion of PBMC to immobilized intercellular adhesion molecule-1 and fibronectin, ligands for LFA-1 and VLA-4, respectively. Stimulation of integrin-mediated cell adhesion by PRL may involve the activation of chemokine receptors, because PRL upregulates the expression of the G-protein-coupled chemokine receptor CXCR3 in PBMC, and pertussis toxin, a specific G-protein inhibitor, blocks PRL stimulation of PBMC adhesion to HUVEC. In addition, PRL stimulates tyrosine phosphorylation pathways leading to leukocyte adhesion. PRL triggered the tyrosine phosphorylation of Janus kinase-2, of signal transducer and activator of transcription-3 and 5, and of the focal adhesion protein paxillin. Furthermore, genistein, a tyrosine kinase inhibitor, blocked PRL-stimulated adhesion of PBMC and Jurkat T-cells to HUVEC. These results suggest that PRL promotes integrin-mediated leukocyte adhesion to endothelial cells via chemokine receptors and tyrosine phosphorylation signaling pathways.
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PMID:Prolactin stimulates integrin-mediated adhesion of circulating mononuclear cells to endothelial cells. 1575 53

Although the G-protein coupled receptor GPR10 is highly expressed in the anterior pituitary, the action of its ligand prolactin-releasing peptide-31 (PrRP) in this tissue is controversial. The present study examined the acute effect of this peptide on prolactin secretion in perifused rat pituitary reaggregate cell cultures from adult male rats. PrRP readily and dose-dependently stimulated prolactin release at concentrations of 10 and 100 nM, although with a magnitude several times lower than that of thyrotropin-releasing hormone. Surprisingly, PrRP inhibited prolactin release at 0.1 and 1 nm in a pertussis toxin-sensitive manner. Inhibition was markedly favoured by long-term culture. Stimulation and inhibition were differentially affected by the presence of hormones during culture: dexamethasone favoured the inhibitory effect and decreased the magnitude of the stimulatory effect, while oestradiol and triiodothyronine strongly reduced stimulation, as well as inhibition. PrRP, even at 1 nm, counteracted the inhibition of prolactin release by dopamine. There was no effect of PrRP on growth hormone release in aggregates cultured either in the absence or presence of hormones. The present results confirm the prolactin-releasing capacity of PrRP at nanomolar doses and reveal a hitherto unrecognized inhibitory activity of this peptide. Furthermore, dopamine inhibition of prolactin release is antagonized by PrRP, irrespective of the PrRP dose.
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PMID:Stimulation and inhibition of prolactin release by prolactin-releasing Peptide in rat anterior pituitary cell aggregates. 1592 43

In previous studies, we demonstrated biphasic purinergic effects on prolactin (PRL) secretion stimulated by an adenosine A2 agonist. In the present study, we investigated the role of the activation of adenosine A1 receptors by (R)-N6-(2-phenylisopropyl)adenosine (R-PIA) at the pituitary level in in vitro PRL secretion. Hemipituitaries (one per cuvette in five replicates) from adult male rats were incubated. Administration of R-PIA (0.001, 0.01, 0.1, 1, and 10 microM) induced a reduction of PRL secretion into the medium in a U-shaped dose-response curve. The maximal reduction was obtained with 0.1 microM R-PIA (mean +/- SEM, 36.01 +/- 5.53 ng/mg tissue weight (t.w.)) treatment compared to control (264.56 +/- 15.46 ng/mg t.w.). R-PIA inhibition (0.01 microM = 141.97 +/- 15.79 vs control = 244.77 +/- 13.79 ng/mg t.w.) of PRL release was blocked by 1 microM cyclopentyltheophylline, a specific A1 receptor antagonist (1 microM = 212.360 +/- 26.560 ng/mg t.w.), whereas cyclopentyltheophylline alone (0.01, 0.1, 1 microM) had no effect. R-PIA (0.001, 0.01, 0.1, 1 microM) produced inhibition of PRL secretion stimulated by both phospholipase C (0.5 IU/mL; 977.44 +/- 76.17 ng/mg t.w.) and dibutyryl cAMP (1 mM; 415.93 +/- 37.66 ng/mg t.w.) with nadir established at the dose of 0.1 microM (225.55 +/- 71.42 and 201.9 +/- 19.08 ng/mg t.w., respectively). Similarly, R-PIA (0.01 microM) decreased (242.00 +/- 24.00 ng/mg t.w.) the PRL secretion stimulated by cholera toxin (0.5 mg/mL; 1050.00 +/- 70.00 ng/mg t.w.). In contrast, R-PIA had no effect (468.00 +/- 34.00 ng/mg t.w.) on PRL secretion stimulation by pertussis toxin (0.5 mg/mL; 430.00 +/- 26.00 ng/mg t.w.). These results suggest that inhibition of PRL secretion after A1 receptor activation by R-PIA is mediated by a Gi protein-dependent mechanism.
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PMID:Adenosine A1 receptor-mediated inhibition of in vitro prolactin secretion from the rat anterior pituitary. 1714 62

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