scholarly journals A Drug-Like Antagonist Inhibits Thyrotropin Receptor–Mediated Stimulation of cAMP Production in Graves' Orbital Fibroblasts

Thyroid ◽  
2012 ◽  
Vol 22 (8) ◽  
pp. 839-843 ◽  
Author(s):  
Susanne Neumann ◽  
Arthur Pope ◽  
Elizabeth Geras-Raaka ◽  
Bruce M. Raaka ◽  
Rebecca S. Bahn ◽  
...  
Keyword(s):  
Thyrotropin Receptor ◽  
Camp Production ◽  
Orbital Fibroblasts ◽  
Stimulation Of

A Drug-like Antagonist Inhibits TSH Receptor-Mediated Stimulation of cAMP Production in Graves’ Orbital Fibroblasts

Thyroid ◽  
2012 ◽  
pp. 120517084830005 ◽  
Author(s):  
Marvin C Gershengorn ◽  
Susanne Neumann ◽  
Arthur Pope ◽  
Elizabeth Geras-Raaka ◽  
Bruce M Raaka ◽  
...  
Keyword(s):  
Tsh Receptor ◽  
Camp Production ◽  
Orbital Fibroblasts ◽  
Stimulation Of

scholarly journals Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation

2005 ◽  
Vol 152 (5) ◽  
pp. 777-784 ◽  
Author(s):  
Patrizia Agretti ◽  
Giuseppina De Marco ◽  
Melissa De Servi ◽  
Claudio Marcocci ◽  
Paolo Vitti ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Autoimmune Disorder ◽  
Ocular Tissue ◽  
Decompression Surgery ◽  
Mrna Levels ◽  
Thyrotropin Receptor ◽  
Camp Production ◽  
Thyroid Associated Ophthalmopathy ◽  
Adipocytic Differentiation ◽  
Orbital Fibroblasts

Objective: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue in the human orbit. Design: The aim of this study was to investigate the thyrotropin receptor (TSHr) expression in orbital fibroblasts from TAO patients undergoing adipocytic differentiation. Methods: Retro-ocular tissue and skin were obtained from five patients undergoing orbital decompression surgery for TAO and placed in culture. Proliferating fibroblasts were subjected to adipocytic differentiation for 10 days. Total RNA was isolated from fibroblasts and was reverse transcribed. TSHr mRNA levels were determined by real-time PCR. cAMP was determined by radioimmunoassay (RIA) after fibroblast incubation with the substances to test. Results: Orbital differentiated fibroblasts became rounded and acquired lipid droplets. The amount of TSHr mRNA in these fibroblasts was higher than fibroblasts not subjected to adipocytic differentiation. Immunocytochemical analysis showed TSHr protein in differentiated orbital fibroblasts. Differentiated orbital fibroblasts stimulated with bovine (b) TSH showed a cAMP production greater than that in paired undifferentiated cultures. A specific thyroid-inhibiting antibody (TBAb) inhibited cAMP production after bTSH challenge, and a thyroid-stimulating antibody (TSAb) stimulated cAMP production in differentiated fibroblasts. Conclusions: We suggest that orbital fibroblasts subjected to adipocytic differentiation increase TSHr expression that responds specifically to bTSH and TSAb stimulation, and to TBAb inhibition.

Prostaglandin E2-histamine in interactions on cAMP, cGMP, and acid production in isolated fundic glands

1982 ◽  
Vol 242 (1) ◽  
pp. G21-G26 ◽  
Author(s):  
R. A. Levine ◽  
K. R. Kohen ◽  
E. H. Schwartzel ◽  
C. E. Ramsay
Keyword(s):  
Prostaglandin E2 ◽  
Acid Secretion ◽  
Acid Production ◽  
Camp Production ◽  
Histamine Stimulation ◽  
Fundic Mucosa ◽  
Biochemical Responses ◽  
Camp Levels ◽  
Camp And Cgmp ◽  
Stimulation Of

Relations among cAMP, cGMP, acid production [measured by the intraglandular accumulation of [14C]aminopyrine (AP)], and prostaglandin E2 (PGE2) activity were studied in isolated glands from rabbit fundic mucosa. AP, cAMP, and cGMP responses to histamine, PGE2, and 3-isobutyl-1-methylxanthine (IMX) were compared with controls. Histamine and PGE2 significantly increased glandular cAMP levels twofold, and histamine and IMX stimulated AP uptake two- to fourfold. PGE2 significantly inhibited both histamine- and IMX-stimulated AP accumulation, but it did not alter basal AP uptake. PGE2 also decreased histamine-stimulated cAMP production but only at a low concentration (10(-7) M). This dose of PGE2 was near to the endogenous PGE2 content found in unstimulated glands (10(-8) M). Intraglandular cGMP levels in unstimulated glands (10(-8) M). Intraglandular cGMP levels were increased by IMX but not by PGE2 or histamine. It is concluded that histamine stimulation of acid secretion is mediated by cAMP, that secretory and biochemical responses to histamine are modulated by PGE2 because PGE2 antagonized histamine-stimulated cAMP and AP uptake, and that the rise in cAMP induced solely by PGE2 appears to be localized within nonparietal cells because PGE2 alone did not stimulate AP accumulation.

MATURATIONAL CHANGES IN SHEEP OVARIAN FOLLICLES: GONADOTROPHIC STIMULATION OF CYCLIC AMP PRODUCTION BY ISOLATED THECA AND GRANULOSA CELLS

1978 ◽  
Vol 89 (1) ◽  
pp. 166-172 ◽  
Author(s):  
T. J. Weiss ◽  
D. T. Armstrong ◽  
J. E. A. McIntosh ◽  
R. F. Seamark
Keyword(s):  
Cyclic Amp ◽  
Granulosa Cells ◽  
Follicle Stimulating Hormone ◽  
Adenosine Monophosphate ◽  
Ovarian Follicles ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Camp Production ◽  
Stimulation Of ◽  
Stimulating Hormone

ABSTRACT Theca and granulosa tissues isolated from sheep ovarian follicles of different sizes were incubated in the presence of human chorionic gonadotrophin (HCG; 5 IU/ml) or follicle stimulating hormone (FSH; 5 μg NIH-FSH-S11/ml) for 40 min. Changes in the total amounts of cyclic 3′,5′-adenosine monophosphate (cAMP) were used as an index of the responsiveness of these preparations to the hormones. Thecal tissue of both large (4–6 mm in diameter) and small (1–3 mm) follicles responded similarly to gonadotrophins. Granulosa cells from small follicles failed to respond to stimulation by HCG. FSH, however, consistently increased cAMP production in comparison with controls or cells treated with HCG. Granulosa cells of large follicles responded to both HCG and FSH.

Selected Contribution: Long-term effects of β2-adrenergic receptor stimulation on alveolar fluid clearance in mice

2002 ◽  
Vol 93 (5) ◽  
pp. 1875-1880 ◽  
Author(s):  
C. Sartori ◽  
X. Fang ◽  
D. W. McGraw ◽  
P. Koch ◽  
M. E. Snider ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Fluid Transport ◽  
Alveolar Fluid Clearance ◽  
Camp Production ◽  
Long Term Effects ◽  
Agonist Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Stimulation Of ◽  
Alveolar Edema

Stimulation of active fluid transport with β-adrenergic receptor (βAR) agonists can accelerate the resolution of alveolar edema. However, chronic βAR-agonist administration may cause βAR desensitization and downregulation that may impair physiological responsiveness to βAR-agonist stimulation. Therefore, we measured baseline and terbutaline- (10−3 M) stimulated alveolar fluid clearance in mice that received subcutaneously (miniosmotic pumps) either saline or albuterol (2 mg · kg−1 · day−1) for 1, 3, or 6 days. Continuous albuterol administration increased plasma albuterol levels (10−5 M), an effect that was associated with 1) a significant decrease in βAR density and 2) attenuation, but not ablation, of maximal terbutaline-induced cAMP production. Forskolin-mediated cAMP-release was unaffected. Continuous albuterol infusion stimulated alveolar fluid clearance on day 1 but did not increase alveolar fluid clearance on days 3 and 6. However, terbutaline-stimulated alveolar fluid clearance in albuterol-treated mice was not reduced compared with saline-treated mice. Despite significant reductions in βAR density and agonist-mediated cAMP production by long-term βAR-agonist exposure, maximal βAR-agonist-mediated increase in alveolar fluid clearance is not diminished in mice.

Mechanism of action of γ-aminobutyric acid on frog melanotrophs

1995 ◽  
Vol 14 (1) ◽  
pp. 1-12 ◽  
Author(s):  
L Desrues ◽  
H Vaudry ◽  
M Lamacz ◽  
M C Tonon
Keyword(s):  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Inhibitory Effect ◽  
Aminobutyric Acid ◽  
Calcium Stores ◽  
Camp Production ◽  
Biphasic Effect ◽  
Camp Levels ◽  
Camp Formation ◽  
Stimulation Of

ABSTRACT We have previously demonstrated that γ-aminobutyric acid (GABA) is a potent regulator of secretory and electrical activity in melanotrophs of the frog pituitary. The aim of the present study was to investigate the intracellular events which mediate the response of melanotrophs to GABA. We first observed that GABA (1–100 μm inhibited both basal and forskolin-stimulated cyclic AMP (cAMP) formation. The inhibitory effect of GABA on cAMP levels was mimicked by the GABAB receptor agonist baclofen (100 μm) and totally abolished by a 4-h pretreatment with pertussis toxin (01 μg/ml). In contrast, the specific GABAA agonist 3-aminopropane sulphonic acid (3APS) did not affect cAMP production. Both GABA and 3APS (100 μm each) induced a biphasic effect on α-MSH release from perifused frog neurointermediate lobes, i.e. a transient stimulation followed by an inhibition of α-MSH secretion. Administration of forskolin (10 μm) prolonged the stimulatory phase and attenuated the inhibitory phase evoked by GABA and 3APS, indicating that cAMP modulates the response of melanotrophs to GABAA agonists. Ejection of 3APS (1 μm) in the vicinity of cultured melanotrophs caused a massive increase in intracellular calcium concentration ([Ca2+]i). The stimulatory effect of 3APS on [Ca2+]i was abolished when the cells were incubated in a chloride-free medium. The formation of inositol trisphosphate was not affected by 3APS, suggesting that the increase in [Ca2+]i cannot be ascribed to mobilization of intracellular calcium stores. ω-Conotoxin did not alter the secretory response of frog neurointermediate lobes to 3APS, while nifedipine blocked the stimulation of α-MSH secretion induced by 3APS. In conclusion, the present data indicate that, in frog pituitary melanotrophs, (i) the stimulatory phase evoked by GABAA agonists can be accounted for by an influx of calcium through L-type calcium channels, (ii) the inhibitory effect evoked by GABAB agonists can be ascribed to inhibition of adenylate cyclase activity and (iii) cAMP attenuates the inhibitory phase evoked by GABAA agonists. Taken together, these data suggest that activation of GABAB receptors may modulate GABAA receptor function.

Modulation of a pacemaker current through Ca2+-induced stimulation of cAMP production

10.1038/10189 ◽  
1999 ◽  
Vol 2 (7) ◽  
pp. 634-641 ◽  
Author(s):  
Anita Lüthi ◽  
David A. McCormick
Keyword(s):  
Camp Production ◽  
Pacemaker Current ◽  
Stimulation Of

scholarly journals Relaxin Stimulates Protein Kinase C ζ Translocation: Requirement for Cyclic Adenosine 3′,5′-Monophosphate Production

2005 ◽  
Vol 19 (4) ◽  
pp. 1012-1023 ◽  
Author(s):  
Bao T. Nguyen ◽  
Carmen W. Dessauer
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Time Course ◽  
Kinase Inhibitors ◽  
Mesangial Cells ◽  
Camp Production ◽  
Protein Levels ◽  
Kinase C ◽  
Phosphoinositide 3 Kinase ◽  
Stimulation Of

Abstract Relaxin is a polypeptide hormone that activates the leucine-rich repeat containing G protein-coupled receptors, LGR7 and LGR8. In an earlier study, we reported that relaxin produces a biphasic time course and the second wave of cAMP is highly sensitive to phosphoinositide-3 kinase inhibitors (LY294002 and wortmannin). LY294002 inhibits relaxin-mediated increases in cAMP production by 40–50% across a large range of relaxin concentrations. Here we show that protein kinase C ζ (PKCζ) is a component of relaxin signaling in THP-1 cells. Sphingomyelinase increases cAMP production due to the release of ceramide, a direct activator of PKCζ. Chelerythrine chloride (a general PKC inhibitor) inhibits relaxin induced cAMP production to the same degree (∼40%) as LY294002. Relaxin stimulates PKCζ translocation to the plasma membrane in THP-1, MCF-7, pregnant human myometrial 1–31, and mouse mesangial cells, as shown by immunocytochemistry. PKCζ translocation is phosphoinositide-3 kinase dependent and independent of cAMP production. Antisense PKCζ oligodeoxynucleotides (PKCζ-ODNs) deplete both PKCζ transcript and protein levels in THP-1 cells. PKCζ-ODNs abolish relaxin-mediated PKCζ translocation and inhibit relaxin stimulation of cAMP by 40%, as compared with mock and random ODN controls. Treatment with LY294002 in the presence of PKCζ-ODNs results in little further inhibition. In summary, we present a novel role for PKCζ in relaxin-mediated stimulation of cAMP.

Metabolic responses of Sertoli cells in culture to various concentrations of follicle stimulating hormone and cholera toxin

1978 ◽  
Vol 56 (9) ◽  
pp. 875-879 ◽  
Author(s):  
Irving B. Fritz ◽  
Michael D. Griswold ◽  
B. Gregory Louis ◽  
Jennifer H. Dorrington
Keyword(s):  
Cholera Toxin ◽  
Sertoli Cells ◽  
Follicle Stimulating Hormone ◽  
Camp Production ◽  
Apparent Paradox ◽  
Maximal Stimulation ◽  
Enriched Cultures ◽  
Estradiol Synthesis ◽  
Stimulation Of ◽  
Stimulating Hormone

The concentration of cholera toxin required for half-maximal stimulation of cAMP production by Sertoli cell enriched cultures (4.48 × 10−2 μg/ml) is greater than that required for half-maximal stimulation of 17β-estradiol synthesis from testosterone (2.34 × 10−4 μg/ml), [3H]thymidine incorporation into DNA (1.48 × 10−5μg/ml), or androgen binding protein production (2.43 × 10−6 μg/ml). The same relative dose response hierarchy was obtained with respect to stimulation of Sertoli cells with follicle stimulating hormone (FSH) preparations. Again, highest concentrations were required to elicit maximal cAMP production. The data are discussed in relation to an apparent paradox: If cAMP is the mediating 'second messenger' following stimulation by FSH or cholera toxin, why should highest concentrations of these agents be required to elicit 50% of maximal cAMP levels?

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