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1.
Science ; 384(6700): 1086-1090, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38843318

RESUMO

Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI 147, a 0.11-solar-mass star. The inner disk has a carbon-rich chemistry; we identified emission from 13 carbon-bearing molecules, including ethane and benzene. The high column densities of hydrocarbons indicate that the observations probe deep into the disk. The high carbon-to-oxygen ratio indicates radial transport of material within the disk, which we predict would affect the bulk composition of any planets forming in the disk.

2.
Nature ; 620(7974): 516-520, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37488359

RESUMO

Terrestrial and sub-Neptune planets are expected to form in the inner (less than 10 AU) regions of protoplanetary disks1. Water plays a key role in their formation2-4, although it is yet unclear whether water molecules are formed in situ or transported from the outer disk5,6. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks7, similar to PDS 70, the first system with direct confirmation of protoplanet presence8,9. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large (approximately 54 AU) planet-carved gap separating an inner and outer disk10,11. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H2 and/or OH, and survival through water self-shielding5. This is also supported by the presence of CO2 emission, another molecule sensitive to ultraviolet photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir12. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.

3.
Osteoporos Int ; 25(2): 543-50, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23912556

RESUMO

UNLABELLED: The Safe Functional Motion test (SFM) was developed to document movement strategies used to perform everyday activities that may increase the risk for osteoporotic fracture. After adjusting for variables known to predict vertebral compression fracture (VCF), baseline score on the SFM was a significant independent predictor of incident VCF at 1- and 3-year follow-ups. INTRODUCTION: Functional movements may contribute to risk for VCF. We hypothesize that scores on the SFM, a performance-based test of physical function, are associated with incident VCF. METHODS: An osteoporosis clinic database was queried for men and women ≥ 50 years with an initial SFM and corresponding data for prevalent VCF, history of injurious falls, femoral neck bone mineral density (fnBMD), osteoporosis medication use, and incident morphometric VCF at 1-year (n = 878) and 3-year follow-ups (n = 503). Multiple logistic regressions, adjusted for gender, age, injurious fall(s), fnBMD, prevalent VCF at baseline, and osteoporosis medication use, were used to determine whether SFM score was associated with incident VCF at follow-up visits. RESULTS: Baseline SFM score was a significant independent predictor of incident VCF at 1-year follow-up (adjusted odds ratio (95 % confidence intervals (CI)) = 0.818 (0.707, 0.948); p < 0.008) and 3-year follow-up (adjusted odds ratio (95 % CI) = 0.728 (0.628, 0.844); p < 0.0001). Baseline fnBMD and osteoporosis medication use were significant predictors at 1-year (p = 0.05 and < 0.0001, respectively) and 3-year (p < 0.01 and 0.001, respectively) follow-ups. At 3-year follow-up, gender and prevalent VCF were also significant predictors (p = 0.003 and 0.007, respectively). CONCLUSIONS: For every 10-point increase in SFM score, the odds of future VCF decreases by 18 % at 1 year and 27 % at 3 years after adjusting for known covariates. The SFM may aid in the identification of modifiable functional risk factors for VCF.


Assuntos
Atividades Cotidianas , Fraturas por Compressão/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Fraturas da Coluna Vertebral/fisiopatologia , Idoso , Densidade Óssea/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Força Muscular/fisiologia , Equilíbrio Postural/fisiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco/métodos , Suporte de Carga/fisiologia
4.
Growth Factors ; 20(3): 141-5, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12519017

RESUMO

We have established a reliable, reproducible and objective growth assay to measure whether leukemia inhibitory factor (LIF) was able to protect tumour-derived cell lines from toxic effects of the chemotherapy agents, cisplatin and paclitaxel. Using this assay, we demonstrated that LIF did not alter the cytotoxic action of these drugs, on a panel of seven cancer cell lines. This was not because of the inactivity of the LIF or because the cell lines did not express components of the LIF receptor. These findings suggest that the potential clinical use of LIF, as a neuroprotective agent, in conjunction with chemotherapy will not interfere with the anti-tumour treatment.


Assuntos
Carcinoma/tratamento farmacológico , Cisplatino/farmacologia , Inibidores do Crescimento/metabolismo , Interleucina-6 , Linfocinas/metabolismo , Paclitaxel/farmacologia , Antígenos CD/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Diferenciação Celular , Divisão Celular , Receptor gp130 de Citocina , Relação Dose-Resposta a Droga , Humanos , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Glicoproteínas de Membrana/metabolismo , RNA Mensageiro/metabolismo , Receptores de Citocinas/metabolismo , Receptores de OSM-LIF , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Células Tumorais Cultivadas
5.
Circ Res ; 88(9): 888-94, 2001 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-11348997

RESUMO

Emerging evidence indicates that reactive oxygen species are important regulators of vascular function. Although NAD(P)H oxidases have been implicated as major sources of superoxide in the vessel wall, the molecular identity of these proteins remains unclear. We recently cloned nox1 (formerly mox-1), a member of a new family of gp91(phox) homologues, and showed that it is expressed in proliferating vascular smooth muscle cells (VSMCs). In this study, we examined the expression of three nox family members, nox1, nox4, and gp91(phox), in VSMCs, their regulation by angiotensin II (Ang II), and their role in redox-sensitive signaling. We found that both nox1 and nox4 are expressed to a much higher degree than gp91(phox) in VSMCS: Although serum, platelet-derived growth factor (PDGF), and Ang II downregulated nox4, they markedly upregulated nox1, suggesting that this enzyme may account for the delayed phase of superoxide production in these cells. Furthermore, an adenovirus expressing antisense nox1 mRNA completely inhibited the early phase of superoxide production induced by Ang II or PDGF and significantly decreased activation of the redox-sensitive signaling molecules p38 mitogen-activated protein kinase and Akt by Ang II. In contrast, redox-independent pathways induced by PDGF or Ang II were unaffected. These data support a role for nox1 in redox signaling in VSMCs and provide insight into the molecular identity of the VSMC NAD(P)H oxidase and its potentially critical role in vascular disease.


Assuntos
Glicoproteínas de Membrana/genética , Músculo Liso Vascular/metabolismo , Animais , Northern Blotting , Linhagem Celular , Células Cultivadas , DNA Antissenso/genética , DNA Complementar/química , DNA Complementar/genética , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Indóis/farmacologia , Maleimidas/farmacologia , Glicoproteínas de Membrana/metabolismo , Dados de Sequência Molecular , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , NADH NADPH Oxirredutases/genética , NADH NADPH Oxirredutases/metabolismo , NADPH Oxidase 1 , NADPH Oxidase 2 , NADPH Oxidase 4 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Oxirredução , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Análise de Sequência de DNA , Transdução de Sinais , Superóxidos/metabolismo , Fatores de Tempo
6.
Cancer Chemother Pharmacol ; 48(6): 429-34, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11800022

RESUMO

PURPOSE: Peripheral neuropathy caused by the anticancer agents cisplatin and paclitaxel is a significant dose-limiting toxicity of these drugs. The growth factor leukaemia inhibitory factor (LIF) has neuroprotectant activity in preclinical models of nerve injury and degeneration and is now in a phase II trial in chemotherapy-induced peripheral neuropathy (CIPN). It is therefore important to ensure that LIF neither inhibits the antitumour activity of these drugs, nor stimulates tumour growth. METHODS: Mature female Dark Agouti rats were implanted subcutaneously with a mammary carcinoma, DAMA. It was confirmed that the tumour expressed LIF receptors by reverse transcriptase polymerase chain reaction. Paclitaxel was administered at a dose of 5 mg/kg daily for 6 days, cisplatin at a dose of 3 mg/kg twice weekly and carboplatin at a dose of 10 mg/kg twice weekly. The effect of LIF on tumour growth and response to chemotherapy was assessed at two doses (2 and 10 microg/kg per day). Peripheral neuropathy was assessed in terms of gait disturbance and tail-flick threshold. RESULTS: Neither dose of LIF stimulated growth of control tumours. Mean tumour volumes were lower on day 14 in all paclitaxel-, cisplatin- and carboplatin-treated groups, compared to controls (ANOVA P<0.001). LIF did not interfere with this antitumour effect. Cisplatin- and paclitaxel-treated groups had developed increasing tail-flick thresholds by day 14. These manifestations of sensory neuropathy were prevented by LIF administration. CONCLUSIONS: These results suggest that LIF may be safely used in human trials as a neuroprotectant for patients receiving cisplatin, paclitaxel and carboplatin without concern for impairment of antitumour effect.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carboplatina/farmacologia , Cisplatino/farmacologia , Inibidores do Crescimento/farmacologia , Interleucina-6 , Linfocinas/farmacologia , Paclitaxel/farmacologia , Animais , Interações Medicamentosas , Feminino , Infusões Parenterais , Injeções Subcutâneas , Fator Inibidor de Leucemia , Neoplasias Mamárias Experimentais , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Ratos
7.
Growth Factors ; 19(3): 153-62, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11811789

RESUMO

We have previously reported the inhibitory effects of oncostatin M (OSM) and leukemia inhibitory factor (LIF) on the proliferation of breast cancer cell lines. In this study, we examined the action of OSM and LIF on normal, non-malignant human breast epithelial cells (HBECs). We demonstrated expression of three components of the OSM receptor; gp130, the leukemia inhibitory factor receptor (LIFRbeta) and the OSM specific receptor (OSMRbeta). Treatment of the normal HBECs with OSM and LIF resulted in inhibition of proliferation, even in the presence of the breast mitogen, epidermal growth factor (EGF), which is required for HBEC growth. The inhibition was associated with a reduction of cells in the S-phase of the cell cycle and an accumulation of cells in G0/G1. These results suggest a previously unrecognised physiological role for these growth factors in the regulation of normal breast epithelium.


Assuntos
Mama/metabolismo , Proteínas de Caenorhabditis elegans , Células Epiteliais/metabolismo , Inibidores do Crescimento/metabolismo , Proteínas de Helminto/metabolismo , Interleucina-6 , Linfocinas/metabolismo , Peptídeos/metabolismo , Antígenos CD/metabolismo , Western Blotting , Ciclo Celular , Divisão Celular , Linhagem Celular , Receptor gp130 de Citocina , Citocinas/biossíntese , Fator de Crescimento Epidérmico/metabolismo , Feminino , Humanos , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Glicoproteínas de Membrana/metabolismo , Oncostatina M , Receptores de Citocinas/metabolismo , Receptores de OSM-LIF , Receptores de Oncostatina M , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
8.
Mol Pharmacol ; 57(3): 460-7, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10692485

RESUMO

The effects of angiotensin II (Ang II) are mediated primarily by Ang II type 1 receptors, which in turn are coupled to heterotrimeric G proteins. After receptor activation, the G(alpha) and G(betagamma) subunits dissociate, contributing to the signaling cascades involving protein kinase C (PKC) activation. Regulators of G protein signaling (RGS proteins) comprise a class of proteins that have been shown to negatively regulate the G(alpha) subunit. We examined which RGS sequences were expressed in vascular smooth muscle cells and which of these were regulated by Ang II. Reverse transcription-polymerase chain reaction showed that of 16 RGS sequences screened, six RGS transcripts (RGS2, 3, 10, 11, and 12 and GAIP) were present. Northern blot analysis demonstrated that RGS3, 10, and 12 and GAIP were not regulated by Ang II at the mRNA level. In contrast, RGS2 mRNA was rapidly and dose dependently increased (395 +/- 24% peak, 45 min) by Ang II but returned to baseline level by 6 to 8 h. Phorbol-12-myristate-13-acetate, a PKC activator, robustly increased RGS2. This signal was attenuated by the PKC inhibitor GF 109203X (50 +/- 4%) and by phorbol-12, 13-dibutyrate-mediated down-regulation of PKC (48 +/- 13%). Tyrosine kinase inhibition and calcium deprivation did not affect the up-regulation of RGS2 mRNA after Ang II stimulation. Actinomycin D treatment inhibited both Ang II- and phorbol-12-myristate-13-acetate-stimulated RGS2 up-regulation, suggesting activation of transcription by these agonists. The stability of RGS2 mRNA did not appear to be affected by Ang II. Thus, RGS2 is a likely candidate for negative regulation of the G proteins coupled to the Ang II type 1 receptor in vascular smooth muscle cells. Regulation of this protein may be of critical importance in modulating the role of Ang II in vascular disease.


Assuntos
Angiotensina II/fisiologia , Regulação da Expressão Gênica , Músculo Liso Vascular/metabolismo , Proteínas RGS/genética , Animais , Cálcio/metabolismo , Células Cultivadas , Masculino , Músculo Liso Vascular/citologia , Proteína Quinase C/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas RGS/biossíntese , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina , Receptores de Angiotensina/efeitos dos fármacos , Receptores de Angiotensina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
9.
Mol Med Today ; 5(9): 406-12, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10462753

RESUMO

Oncostatin M (OSM) is a member of the interleukin 6 (IL-6) family of cytokines and was originally identified by its ability to inhibit proliferation of melanoma cells but augment the growth of normal fibroblasts. OSM has pleiotropic effects on many different cell types, but here we focus on its ability to inhibit the proliferation of cell lines derived from several tumour types, including breast carcinoma, ovarian cancer, melanoma, glioma and lung carcinoma. The inhibition of proliferation of several cancer cell lines by OSM is associated with alterations in cellular morphology and with phenotypic changes that are consistent with the induction of differentiation of these cells. These observations raise the possibility that OSM could have therapeutic potential.


Assuntos
Antineoplásicos/farmacologia , Peptídeos/metabolismo , Transdução de Sinais , Animais , Antineoplásicos/metabolismo , Humanos , Neoplasias/terapia , Oncostatina M , Peptídeos/farmacologia , Peptídeos/fisiologia , Fenótipo , Transdução de Sinais/efeitos dos fármacos
10.
Int J Cancer ; 75(1): 64-73, 1998 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-9426692

RESUMO

We have recently described the action of Oncostatin M (OSM) to inhibit the proliferation of breast cancer cells. In this study we examined the action of OSM on 2 breast cancer cell lines to further characterize the nature of OSM inhibition of cellular proliferation. Treatment with OSM for 6 days resulted in an approximately 2- to 5-fold decrease in cell number, which was independent of estrogen receptor status. Consistent with this, colony formation was reduced to approximately 50% when cells were exposed to OSM in primary agar cultures. Clonogenicity was further inhibited following 7 days treatment with OSM in monolayer cultures: the total number of clonogenic cells was suppressed approximately 10-fold. Analysis of cell cycle status in OSM-treated cells demonstrated a 40% reduction in the proportion of cells in S phase within 12 hr, with an increase in cells in G0/G1. After 6 days, there was a 10-fold reduction in the absolute number of cells in S phase in OSM-treated cultures. These changes were associated with striking changes in cellular morphology, including disruption of intercellular junctions and the production of lipid droplets. There was a 5-fold increase of c-fos and c-myc mRNA within 30 min of commencing treatment with OSM. In addition, in the ER positive cells there was a decrease in ER mRNA (evident within approximately 2 hr) and ER protein expression following treatment with OSM. Conversely, there was a 5-fold increase in epidermal growth factor receptor (EGFR) mRNA within 4 hr, and a 2.5-fold rise in mRNA for transforming growth factor alpha (TGF alpha). Thus, the inhibition of breast cancer cells by OSM was associated with decreased clonogenicity, a decrease in S phase cells and a variety of phenotypic changes, all consistent with the induction of differentiation.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Diferenciação Celular/efeitos dos fármacos , Inibidores do Crescimento/farmacologia , Peptídeos/farmacologia , Transativadores , Contagem de Células/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Ciclinas/efeitos dos fármacos , Ciclinas/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Genes fos/efeitos dos fármacos , Genes myc/efeitos dos fármacos , Substâncias de Crescimento/metabolismo , Humanos , Oncostatina M , RNA Mensageiro/metabolismo , Receptores de Fatores de Crescimento/efeitos dos fármacos , Receptores de Fatores de Crescimento/metabolismo , Fator de Transcrição STAT3 , Células Tumorais Cultivadas/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco
11.
Clin Exp Pharmacol Physiol ; 24(9-10): 680-5, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9315369

RESUMO

1. The effects of indomethacin (an inhibitor of prostaglandin synthesis) on the renal responses to epidermal growth factor (EGF) were investigated in conscious sheep. 2. Ewes (n = 5 per group) received an i.v. saline infusion (150 mL/day) for days 1-8, followed by either vehicle control, 15 micrograms/h EGF, 2 mg/kg per day indomethacin or 15 micrograms/h EGF with 2 mg/kg per day indomethacin in 150 mL/day saline, i.v., over days 9-12. All ewes subsequently received an i.v. saline infusion (150 mL/day) over days 13-20. 3. Polydipsia, diuresis, transient natriuresis and reduced urine osmolality occurred during EGF treatment alone. There was no effect of EGF on fluid balance, plasma electrolyte or hormone concentrations, plasma osmolality or haematocrit or on the urinary excretion of potassium. 4. Simultaneous infusion of indomethacin with EGF attenuated (P < 0.05) the stimulatory effects of EGF infusion alone on urine volume, water intake, natriuresis and urine osmolality. 5. We conclude that prostaglandins may be involved in the diuretic/natriuretic effects of EGF, but may not be the sole mechanism involved.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Fator de Crescimento Epidérmico/farmacologia , Indometacina/farmacologia , Rim/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/sangue , Apetite/efeitos dos fármacos , Diurese/efeitos dos fármacos , Fator de Crescimento Epidérmico/sangue , Feminino , Indometacina/sangue , Natriurese/efeitos dos fármacos , Prostaglandinas/metabolismo , Ovinos , Micção/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
12.
Am J Physiol ; 272(6 Pt 2): R1853-61, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9227600

RESUMO

Epidermal growth factor (EGF) has been shown to induce a renal diuresis and natriuresis in sheep and stimulate prostaglandin synthesis from inner rat medullary collecting duct cells in culture. The aims of our study were 1) to investigate whether the renal effects of intravenous infusion of EGF were species specific and 2) to determine the mechanism of these effects by studying the interaction between EGF and indomethacin (a prostaglandin synthase inhibitor) in the conscious rat. Sprague-Dawley rats received intravenous infusions of either 0.9% saline or 0.2 or 2.0 micrograms EGF.kg-1.h-1 over a 6-day period after an initial baseline period. Infusion of 2.0 micrograms EGF.kg-1.h-1 caused an increase in urine volume (baseline: 5.5 +/- 0.2 ml to day 5: 9.0 +/- 0.4 ml, P < 0.01) and corresponding polydipsia, but not natriuresis. Administration of indomethacin with 2.0 micrograms EGF.kg-1.h-1 attenuated (P < 0.05) the diuretic (day 5 EGF + vehicle: 12.2 +/- 1.1 ml vs. EGF + indomethacin: 8.7 +/- 0.9 ml) and polydipsic effects of EGF. These studies demonstrate that intravenous infusion of EGF causes a diuretic effect in rats without natriuresis and that prostaglandins play a role in the diuretic effect of EGF in the rat.


Assuntos
Líquidos Corporais/metabolismo , Eletrólitos/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Animais , Sangue/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diuréticos/farmacologia , Eletrólitos/urina , Fator de Crescimento Epidérmico/urina , Taxa de Filtração Glomerular/efeitos dos fármacos , Indometacina/farmacologia , Antagonistas de Prostaglandina/farmacologia , Ratos , Ratos Sprague-Dawley
13.
Kidney Int ; 45(4): 1028-36, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8007572

RESUMO

Since EGF causes diuresis through a renal action and may antagonize the hydroosmotic effect of AVP in vitro we investigated the antagonistic action of EGF with AVP in vivo and the mechanism of the antagonism in vitro. Conscious ewes received i.m. injections of a selective AVP V2-receptor agonist (1-desamino, D-Arg8 vasopressin acetate, DDAVP) every 12 hours for days 5 to 16. All ewes received an i.v. isotonic saline infusion (100 ml/day) for days 1 to 8 and days 13 to 16, and i.v. EGF in 100 ml saline/day at doses of 0 (N = 8) or 10 (N = 8) micrograms/hr for days 9 to 12. DDAVP reduced both urine volume and water intake, and increased urine osmolality. In contrast, simultaneous infusion of EGF reversed the DDAVP-induced responses, resulting in a transient negative fluid balance, kaliuresis and a transient natriuresis (all P < 0.05). When EGF treatment ceased, the effects of DDAVP treatment alone gradually became apparent. From the in vitro studies, the AVP-related peptides displaced specific AVP V1- and V2-receptor antagonist radioligands from rat renal inner medullary membranes, whereas EGF had no effect. However, EGF antagonized AVP V2-stimulated cAMP production in a dose-dependent way (IC50 = 2 x 10(-7) M). Therefore, the diuretic effect of EGF is not via direct antagonism of the antidiuretic AVP V2-receptor but seems mediated by inhibition of the antidiuretic AVP V2-receptor second messenger system.


Assuntos
Desamino Arginina Vasopressina/antagonistas & inibidores , Fator de Crescimento Epidérmico/farmacologia , Animais , Arginina Vasopressina/metabolismo , AMP Cíclico/metabolismo , Diurese/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos dos fármacos , Concentração Osmolar , Ratos , Ratos Sprague-Dawley , Receptores de Vasopressinas/metabolismo , Sistemas do Segundo Mensageiro , Ovinos , Equilíbrio Hidroeletrolítico
14.
Clin Exp Pharmacol Physiol ; 21(3): 243-7, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8076430

RESUMO

1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (cAMP) production was inhibited by epidermal growth factor (IC50 2 x 10(-7) mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system.


Assuntos
Arginina Vasopressina/metabolismo , Arginina Vasopressina/farmacologia , Fator de Crescimento Epidérmico/fisiologia , Medula Renal/efeitos dos fármacos , Medula Renal/metabolismo , Adenilil Ciclases/metabolismo , Adenilil Ciclases/fisiologia , Angiotensina II/farmacologia , Animais , Arginina Vasopressina/antagonistas & inibidores , Ligação Competitiva , AMP Cíclico/biossíntese , Interações Medicamentosas , Feminino , Medula Renal/fisiologia , Membranas/efeitos dos fármacos , Membranas/metabolismo , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Receptores de Vasopressinas/metabolismo , Receptores de Vasopressinas/fisiologia , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Sistemas do Segundo Mensageiro/fisiologia
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