EFFECT OF IODIDE ON THE ADENYL CYCLASE SYSTEM OF THE MOUSE THYROID IN VIVO

1978 ◽  
Vol 88 (3) ◽  
pp. 517-527 ◽  
Author(s):  
C. Saddok ◽  
M. Gafni ◽  
J. Gross
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Iodine Content ◽  
Adenosine Monophosphate ◽  
Iodine Intake ◽  
Adenyl Cyclase ◽  
Camp Accumulation ◽  
Adenyl Cyclase Activity ◽  
Pre Treatment ◽  
Highly Correlated

ABSTRACT Iodide, administered to mice either acutely or chronically, depressed the thyroidal cyclic adenosine monophosphate (cAMP) response to 20 mU bovine TSH. When iodide was administered acutely there was a 60% reduction in the cAMP accumulation after 100 μg, or 1 μg KI given to mice on normal iodine diet (NID), or low iodine diet (LID), respectively. When iodide was administered chronically by supplementing the LID with graded doses of KI for 11 days, the cAMP response to TSH was found to be inversely related to the dietary iodine. Inhibition occurred after 5 μg KI, a dose similar to the daily iodine intake. Iodide depressed, but did not abolish, the thyroidal cAMP response to TSH. Iodide had no effect on phosphodiesterase activity, whereas thyroidal adenyl cyclase activity was diminished by the prior administration of 100 μg KI. The iodide effect was abolished by pre-treatment with methylmercaptoimidazole i.e. the inhibition is related to iodide oxidation. The newly organified thyroidal iodine (NOTI), formed at 2 h from 0.1–1000 μg KI was determined. The amount of NOTI was highly correlated to the degree of inhibition, irrespective of the iodine content of the diet. This relationship was continuous up to 100 ng NOTI and 70% inhibition, which are the maximal values obtained for NOTI formation and inhibition of cAMP accumulation. These plateau levels were reached with 100 or 1 μg KI in mice on NID or LID, respectively. These results indicate that the inhibitor is an iodinated substance whose intrathyroidal formation is quantitatively parallel to, or a part of NOTI.

A Study of the Neurohumoral Control of Glycolysis in the Mouse Brain in vivo: Role of Noradrenaline and Dopamine

1975 ◽  
Vol 30 (5-6) ◽  
pp. 385-391 ◽  
Author(s):  
B. E. Leonard
Keyword(s):  
Mouse Brain ◽  
Sodium Fluoride ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Adenyl Cyclase ◽  
Membrane Bound ◽  
Adenyl Cyclase System ◽  
Neurohumoral Control

Abstract Noradrenaline, Dopamine, Glycolysis, Adenyl Cyclase Intraventricularly injected noradrenaline, dopamine and isoprenaline increased glycolysis as shown by the decrease in the concentration of “free” glycogen and increase in the concentration of lactate. The effects of noradrenaline and isoprenaline were reduced in mice which had been pretreated with α-methyl-p-tyrosine. ʟᴅ-Propranolol blocked the increase in glycolysis caused by noradrenaline, isoprenaline, sodium fluoride and analogues of 3,5-cyclic adenosine monophosphate. It is suggested that the results of this investigation can be explained by the various drugs and neurohormones acting on the adenyl cyclase system in vivo, either by blocking the action of the neurohormone on the membrane bound enzyme or monophosphate on glycolysis.

scholarly journals Pharmacological and genetic activation of cAMP synthesis disrupts cholesterol utilization in Mycobacterium tuberculosis

2021 ◽  
Author(s):  
Kaley M. Wilburn ◽  
Christine R. Montague ◽  
Bo Qin ◽  
Ashley K. Woods ◽  
Melissa S. Love ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Adenylyl Cyclase ◽  
Cholesterol Metabolism ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Signaling ◽  
Camp Synthesis ◽  
Pharmacokinetic Properties ◽  
Bacterial Utilization

There is a growing appreciation for the idea that bacterial utilization of host-derived lipids, including cholesterol, supports Mycobacterium tuberculosis (Mtb) pathogenesis. This has generated interest in identifying novel antibiotics that can disrupt cholesterol utilization by Mtb in vivo. Here we identify a novel small molecule agonist (V-59) of the Mtb adenylyl cyclase Rv1625c, which stimulates 3’, 5’-cyclic adenosine monophosphate (cAMP) synthesis and inhibits cholesterol utilization by Mtb. Similarly, using a complementary genetic approach that induces bacterial cAMP synthesis independent of Rv1625c, we demonstrate that inducing cAMP synthesis is sufficient to inhibit cholesterol utilization in Mtb. Although the physiological roles of individual adenylyl cyclase enzymes in Mtb are largely unknown, here we demonstrate that the transmembrane region of Rv1625c is required for cholesterol metabolism. Finally, in this work the pharmacokinetic properties of Rv1625c agonists are optimized, producing an orally-available Rv1625c agonist that impairs Mtb pathogenesis in infected mice. Collectively, this work demonstrates a novel role for Rv1625c and cAMP signaling in controlling cholesterol metabolism in Mtb and establishes that cAMP signaling can be pharmacologically manipulated for the development of new antibiotic strategies.

Lithium administration and phosphate excretion

1976 ◽  
Vol 231 (4) ◽  
pp. 1140-1146 ◽  
Author(s):  
JA Arruda ◽  
JM Richardson ◽  
JA Wolfson ◽  
L Nascimento ◽  
DR Rademacher ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Renal Cortex ◽  
Cyclic Adenosine Monophosphate ◽  
Fractional Excretion ◽  
Adenosine Monophosphate ◽  
Adenyl Cyclase ◽  
Phosphate Excretion ◽  
Camp System

The phosphaturic effect of parathyroid hormone (PTH), cyclic adenosine monophosphate (cAMP), acetazolamide (Az), and HCO3 loading was studied in normal, thyroparathyroidectomized (TPTX), and Li-treated dogs. PTH administration to normal animals markedly increased fractional excretion (F) of PO4 but had a blunted effect on FPO4 in the Li-treated animals. Cyclic AMP likewise markedly increased FPO4 in the normal animals but had a markedly blunted effect in the Li-treated animals. Az led to a significant increase in FNa, FHCO3, and FPO4 in the normal animals. In the Li-treated dogs, Az induced a significant natriuresis and bicarbonaturia but failed to increase phosphaturia. HCO3 loading in normal dogs caused a significant phosphaturia while having little effect on FPO4 in Li-treated dogs. HCO3 loading to TPTX dogs was associated with a lower FPO4 as compared to normal HCO3-loaded animals. These data suggest that Li administration not only blocks the adenyl cyclase-cAMP system in the renal cortex, but it may also interfere with a step distal to the formation of cAMP, since the phosphaturic effect of both PTH and cAMP was markedly diminished in Li-treated animals.

scholarly journals Mel1c Mediated Monochromatic Light-Stimulated IGF-I Synthesis through the Intracellular Gαq/PKC/ERK Signaling Pathway

2019 ◽  
Vol 20 (7) ◽  
pp. 1682
Author(s):  
Shujie Ning ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong ◽  
Yaoxing Chen
Keyword(s):  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Monochromatic Light ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Erk Signaling ◽  
Sham Operation ◽  
Intracellular Signaling Pathway ◽  
Igf I

Previous studies have demonstrated that monochromatic light affects plasma melatonin (MEL) levels, which in turn regulates hepatic insulin-like growth factor I (IGF-I) secretion via the Mel1c receptor. However, the intracellular signaling pathway initiated by Mel1c remains unclear. In this study, newly hatched broilers, including intact, sham operation, and pinealectomy groups, were exposed to either white (WL), red (RL), green (GL), or blue (BL) light for 14 days. Experiments in vivo showed that GL significantly promoted plasma MEL formation, which was accompanied by an increase in the MEL receptor, Mel1c, as well as phosphorylated extracellular regulated protein kinases (p-ERK1/2), and IGF-I expression in the liver, compared to the other light-treated groups. In contrast, this GL stimulation was attenuated by pinealectomy. Exogenous MEL elevated the hepatocellular IGF-I level, which is consistent with increases in cyclic adenosine monophosphate (cAMP), Gαq, phosphorylated protein kinase C (p-PKC), and p-ERK1/2 expression. However, the Mel1c selective antagonist prazosin suppressed the MEL-induced expression of IGF-I, Gαq, p-PKC, and p-ERK1/2, while the cAMP concentration was barely affected. In addition, pretreatment with Ym254890 (a Gαq inhibitor), Go9863 (a PKC inhibitor), and PD98059 (an ERK1/2 inhibitor) markedly attenuated MEL-stimulated IGF-I expression and p-ERK1/2 activity. These results indicate that Mel1c mediates monochromatic GL-stimulated IGF-I synthesis through intracellular Gαq/PKC/ERK signaling.

Neurohormones on Brain Adenyl Cyclase Activity in vivo

1971 ◽  
Vol 233 (43) ◽  
pp. 280-281 ◽  
Author(s):  
W. S. CHOU ◽  
A. K. S. HO ◽  
H. H. LOH
Keyword(s):  
Adenyl Cyclase ◽  
Cyclase Activity ◽  
Adenyl Cyclase Activity

239 USE OF CYCLIC ADENOSINE MONOPHOSPHATE MODULATORS IN IN VITRO PRODUCTION OF BOVINE EMBRYOS

2015 ◽  
Vol 27 (1) ◽  
pp. 209
Author(s):  
T. Fanti ◽  
N. M. Ortega ◽  
R. Garaguso ◽  
M. J. Franco ◽  
C. Herrera ◽  
...  
Keyword(s):  
Phosphodiesterase Inhibitor ◽  
Basal Medium ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Control Group ◽  
Hatching Rate ◽  
Bovine Embryos ◽  
Oocyte Competence

In vitro embryo production systems (IVP) try to emulate and enhance molecular events that occur in in vivo reproductive systems in order to increase, not only the number of embryos generated, but also their quality. Despite advances, IVP processes are still inefficient compared with in vivo systems. Several studies have attributed this deficiency to a lack of oocyte competence due to spontaneous premature resumption of meiotic maturation in the oocyte following the removal from its follicular environment. Therefore, our objective was to increase oocyte competence avoiding premature resumption of meiosis by using cyclic adenosine monophosphate modulators. Cumulus-oocyte complexes (COC) were obtained from ovaries of slaughterhouses, washed, and randomly allocated in 2 culture systems. Oocytes in the control group (IVM) were cultured for a period of 24 h in basal medium TCM-199 with EGF (1 µg mL–1) supplemented with rhFSH (25 mIU mL–1). Oocytes in the biphasic in vitro maturation (b-IVM) group were cultured for 2 h in a basal medium supplemented with a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 500 µM), and an activator of adenylate cyclase (forskolin, 100 µM). Subsequently, COC were washed and cultured in basal medium supplemented with cilostamide (20 µM) and rhFSH (25 mIU mL–1) for 24 h. Maturation rates were analysed and IVF was performed with a dose of 1 × 106 sperm cells mL–1 in IVF-SOF medium. The presumptive zygotes were cultured in continuous-single-culture medium (Irvine) supplemented with 8 mg mL–1 of BSA until they reached the blastocyst stage. No significant differences in maturation, cleavage, and cryotolerance were observed between b-IVM and IVM groups (P > 0.05; Table 1). This study showed that b-IVM produced a significant increase in IVP compared with the control (IVM) at Days 7 and 8 (P < 0.01). Blastocyst hatching rate was significant (P < 0.05) for both treatment and day of analysis. The b-IVM group yielded an increase of 10 and 7.5% at Days 7 and 8, respectively, of IVP. The biphasic maturation showed an improvement in quality regarding the control group, in the timing analysis of production, and hatching percentages, and these results show that the use of cyclic adenosine monophosphate modulators in the oocyte maturation process enhances oocyte competence, which is reflected in increased productivity and embryo quality. We propose this treatment as an alternative to the standard protocols currently used in IVP of bovine embryos. Table 1.Effect of treatment on maturation, cleavage, and cryotolerance

159 EFFECT OF 3-ISOBUTYL-1-METHYLXANTHINE (IBMX) ON THE GERMINAL VESICLE STAGE OF PORCINE OOCYTES DURING OOCYTE COLLECTION IN VITRO

2014 ◽  
Vol 26 (1) ◽  
pp. 193
Author(s):  
R. Appeltant ◽  
J. Beek ◽  
D. Maes ◽  
A. Van Soom
Keyword(s):  
Germinal Vesicle ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cumulus Cells ◽  
Guanosine Monophosphate ◽  
Developmental Competence ◽  
Meiotic Arrest ◽  
Oocyte Collection

When using modern maturation conditions for in vitro maturation, pig oocytes yield ~20% blastocysts only. One problem is that cumulus cells, which are normally connected with the immature oocyte by cellular projections penetrating through the zona pellucida and with the oolemma via gap junctions, are prematurely losing these connections after the cumulus–oocyte complex is removed from the follicle. The oocyte possesses a type 3 phosphodiesterase, which degrades 3′,5′-cyclic adenosine monophosphate (cAMP), and this activity is inhibited by supply of 3′,5′-cyclic guanosine monophosphate (cGMP) to the oocyte via the cumulus cells. Consequently, cAMP levels, which are typically high during early stages of oocyte maturation in vivo, decrease, leading to spontaneous nuclear maturation and oocytes of low developmental competence. Therefore, the maintenance of these cumulus-oocyte connections is important to keep cAMP high and the oocyte under meiotic arrest. One way to prevent this drop in cAMP is using N6, 2′-o-dibutyryladenosine 3′,5′-cyclic monophosphate sodium (dbcAMP) that causes an arrest at germinal vesicle (GV) stage II (Funahashi et al. 1997 Biol. Reprod. 57, 49–53). Another option is collecting the oocytes in a medium containing the phoshodiesterase inhibitor, IBMX. The present study investigated the influence of IBMX on the progression of the GV of the oocyte after collection, just before the start of the maturation procedure. The GV stage was defined according to Sun et al. (2004 Mol. Reprod. Dev. 69, 228–234). In parallel with the findings on dbcAMP, we hypothesised an arrest at GV II by the presence of IBMX during collection. One group of oocytes were collected in HEPES-buffered TALP without IBMX (n = 375) and another group in the same medium containing 0.5 mM IBMX (n = 586). An average incubation time of 140 min was applied in both groups, and 3 replicates were performed. The proportions of oocytes before or at GV II and beyond GV II were compared in both groups using logistic regression analysis. The proportion of oocytes was included as dependent variable and group (IBMX addition or not) as independent variable. Replicate was also included in the model. The proportion of oocytes before or at GV II was not statistically significant between the group without and the group with IBMX (59.2 v. 58.7% respectively; P > 0.05). In conclusion, the use of IBMX during oocyte collection did not influence the state of the germinal vesicle of the oocyte during collection, indicating that IBMX did not cause a meiotic arrest in the oocytes during collecting in vitro.

Effect of P1-purinergic agonist on thyrotropin stimulation of H2O2 generation in FRTL-5 and porcine thyroid cells

1994 ◽  
Vol 130 (2) ◽  
pp. 180-186 ◽  
Author(s):  
Ulla Björkman ◽  
Ragnar Ekholm
Keyword(s):  
Adenylate Cyclase ◽  
Primary Culture ◽  
Purinergic Receptor ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Accumulation ◽  
High Concentration ◽  
Thyroid Cells ◽  
H2o2 Generation ◽  
Stimulation Of

Björkman U, Ekholm R. Effect of P1-purinergic agonist on thyrotropin stimulation of H2O2 generation in FRTL-5 and porcine thyroid cells. Eur J Endocrinol 1994;130:180–6. ISSN 0804–4643 Our previous studies have shown that the generation of H2O2 in FRTL-5 thyroid cells is regulated via both the adenylate cyclase/cyclic adenosine monophosphate (cAMP) and Ca2+/phosphatidylinositol pathway: thyrotropin (TSH) stimulates H2O2 generation through both pathways, via the former at a low concentration and via the latter at a high concentration. In porcine thyrocytes in primary culture H2O2 generation is stimulated only via the Ca2+/phosphatidylinositol route. In the present study we explored the effect of a P1-purinergic agonist (phenylisopropyladenosine, PIA) on stimulations induced by TSH and by adenosine triphosphate (ATP), an activator of the Ca2+/phosphatidylinositol cascade via the P2-purinergic receptor. In FRTL- 5 cells, PIA potentiated H2O2 generation stimulated by TSH at 10U/l (but not at 1 U/l), Ca2+ mobilization induced by TSH and Ca2+ mobilization induced by ATP at 1 μmol/l (but not 10 μmol/l). Phenylisopropyladenosine strongly inhibited TSH-induced cAMP accumulation in FRTL-5 cells. In pig thyrocytes, PIA had no effect on H2O2 generation stimulated by TSH or ATP and no effect on ATP-stimulated Ca2+ mobilization. Also, PIA did not inhibit TSH-stimulated cAMP accumulation in pig thyrocytes, and by itselfhad no effecton H2O2 generation or Ca2 + mobilization. Thus, in FRTL-5 cells, but not in porcine thyrocytes, PIA modulates TSH-stimulated H2O2 generation by enhancing the Ca2+/phosphatitylinositol route and inhibiting the adenylate cyclase/cAMP route of the TSH signal. The net result of this modulation apparently depends on the balance between inhibition of the cAMP route and enhancement of the Ca2+ route. This may explain the lack of potentiation observed by 1 U/1 TSH. Ragnar Ekholm, Department of Anatomy, Medicinaregatan 3, S-413 90 Göteborg, Sweden

Cyclic Adenosine Monophosphate Stimulation of Mucociliary Activity in the Upper Airways in Vivo

1995 ◽  
Vol 104 (5) ◽  
pp. 388-393 ◽  
Author(s):  
Anders Cervin ◽  
Sven Lindberg ◽  
Jan Dolata ◽  
Ulf Mercke
Keyword(s):  
Upper Airway ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Airway Disease ◽  
Maxillary Artery ◽  
Dibutyryl Camp ◽  
Upper Airways ◽  
Maximum Increase ◽  
Xanthine Derivatives

Xanthine derivatives are known to accelerate mucociliary transport in the lower airways, probably by preventing degradation of cyclic adenosine monophosphate (cAMP) and thereby increasing its intracellular concentration. The purpose of this study was to investigate the effects of cAMP on mucociliary activity in the upper airways. The effect on the mucociliary activity in the rabbit maxillary sinus of the xanthine derivatives theophylline and enprophylline was compared to that of the cAMP analog dibutyryl cAMP. The compounds were administered into the maxillary artery, and the response was recorded with a photoelectric technique. Infusions of theophylline (1.0 and 10 mg/kg) increased mucociliary activity (22.8% ± 5.9%, n = 6, and 21.6% ± 4.9%, n = 7, p < .05, respectively). Infusions of enprophylline (1.0 and 10.0 mg/kg) accelerated mucociliary activity (at the highest dosage tested, 24.3% ± 4.1%). Infusions of dibutyryl cAMP (0.1 and 1.0 mg/kg) stimulated mucociliary activity, with the maximum increase (20.1% ± 3.0%, n = 13, p < .05) being observed at a dosage of 0.1 mg/kg. The infused substances increased mucociliary activity within 1 minute after the start of the infusion, the duration of the response being approximately 20 minutes for theophylline, 22 minutes for enprophylline, and 12 minutes for dibutyryl cAMP. The present results support the view that cAMP is involved in regulating mucociliary activity in the upper airways. It remains to be elucidated whether xanthines such as theophylline and enprophylline are beneficial in upper airway disease in which mucociliary function is impaired (eg, chronic sinusitis).

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