scholarly journals Synergistic stimulation of Ca+ uptake by glucagon and Ca2+-mobilizing hormones in the perfused rat liver. A role for mitochondria in long-term Ca2+ homoeostasis

1986 ◽  
Vol 238 (3) ◽  
pp. 653-661 ◽  
Author(s):  
J G Altin ◽  
F L Bygrave
Keyword(s):  
Cyclic Amp ◽  
Calcium Content ◽  
Fold Increase ◽  
Maximal Response ◽  
Similar Response ◽  
Long Term Effects ◽  
Low Concentrations ◽  
Order Of Magnitude ◽  
Stimulation Of

A perfused liver system incorporating a Ca2+-sensitive electrode was used to study the long-term effects of glucagon and cyclic AMP on the mobilization of Ca2+ induced by phenylephrine, vasopressin and angiotensin. At 1.3 mM extracellular Ca2+ the co-administration of glucagon (10 nM) or cyclic AMP (0.2 mM) and a Ca2+-mobilizing hormone led to a synergistic potentiation of Ca2+ uptake by the liver, to a degree which was dependent on the order of hormone administration. A maximum net amount of Ca2+ influx, corresponding to approx. 3800 nmol/g of liver (the maximum rate of influx was 400 nmol/min per g of liver), was induced when cyclic AMP or glucagon was administered about 4 min before vasopressin and angiotensin. These changes are over an order of magnitude greater than those induced by Ca2+-mobilizing hormones alone [Altin & Bygrave (1985) Biochem. J. 232, 911-917]. For a maximal response the influx of Ca2+ was transient and was essentially complete after about 20 min. Removal of the hormones was followed by a gradual efflux of Ca2+ from the liver over a period of 30-50 min; thereafter, a similar response could be obtained by a second administration of hormones. Dose-response measurements indicate that the potentiation of Ca2+ influx by glucagon occurs even at low (physiological) concentrations of the hormone. By comparison with phenylephrine, the stimulation of Ca2+ influx by vasopressin and angiotensin is more sensitive to low concentrations of glucagon and cyclic AMP, and can be correlated with a 20-50-fold increase in the calcium content of mitochondria. The reversible uptake of such large quantities of Ca2+ implicates the mitochondria in long-term cellular Ca2+ regulation.

scholarly journals Long-term effect of cyclic AMP on N-glycosylation is caused by an increase in the activity of the cis-prenyltransferase

1996 ◽  
Vol 316 (2) ◽  
pp. 575-581 ◽  
Author(s):  
Matthias KONRAD ◽  
Wolfgang E. MERZ
Keyword(s):  
Cyclic Amp ◽  
Kinase Activity ◽  
Fold Increase ◽  
Term Effect ◽  
Long Term Effect ◽  
Choriocarcinoma Cells ◽  
Specific Stimulation ◽  
Stimulation Of ◽  
In Cells

Previously we have shown that long-term pretreatment of JEG-3 choriocarcinoma cells with 8-bromo-cAMP increases the capacity for N-glycosylation that was caused by an 8–10-fold enlargement of the dolichol pyrophosphoryl oligosaccharide (Dol-PP-oligosaccharide) pool [Konrad and Merz (1994) J. Biol. Chem. 269, 8659–8666]. The factors involved in the effect of cAMP on synthesis of Dol-PP-oligosaccharide are investigated here. The GlcNAc transfer to dolichol phosphate (Dol-P) was found to be unaffected by pretreatment with 8-bromo-cAMP. By measuring the uptake of [3H]mevalonate, a 20-fold increase in the incorporation of the label into Dol-P was observed in the cells treated with 8-bromo-cAMP. Under the same conditions, the synthesis of dolichol was enhanced 60-fold. However, the incorporation of the radioactivity into cholesterol was not increased in the JEG-3 cells pretreated with 8-bromo-cAMP, which suggests a specific stimulation of the dolichol/Dol-P pathway by cAMP. The cis-prenyltransferase activity was found to be increased 10-fold in cells pretreated with 8-bromo-cAMP. Dolichol kinase activity was unaffected by stimulation with 8-bromo-cAMP. The present study suggests that the larger glycosylation capacity in JEG-3 cells treated with 8-bromo-cAMP is caused by an increase in the microsomal cis-prenyltransferase activity.

Electrical stimulation of referred sensation area alleviates phantom limb pain

2021 ◽  
pp. 1-10
Author(s):  
Michihiro Osumi ◽  
Daisuke Shimizu ◽  
Yuki Nishi ◽  
Shu Morioka
Keyword(s):  
Electrical Stimulation ◽  
Single Case ◽  
Phantom Limb Pain ◽  
Phantom Limb ◽  
Long Term Effects ◽  
Limb Pain ◽  
Short Term ◽  
Analgesic Effects ◽  
Stimulation Of

Background: Patients with brachial plexus avulsion (BPA) usually experience phantom sensations and phantom limb pain (PLP) in the deafferented limb. It has been suggested that evoking the sensation of touch in the deafferented limb by stimulating referred sensation areas (RSAs) on the cheek or shoulder might alleviate PLP. However, feasible rehabilitation techniques using this approach have not been reported. Objective: The present study sought to examine the analgesic effects of simple electrical stimulation of RSAs in BPA patients with PLP. Methods: Study 1: Electrical stimulation of RSAs for 60 minutes was conducted for six BPA patients suffering from PLP to examine short-term analgesic effects. Study 2: A single case design experiment was conducted with two BPA patients to investigate whether electrical stimulation of RSAs was more effective for alleviating PLP than control electrical stimulation (electrical stimulation of sites on side opposite to the RSAs), and to elucidate the long-term effects of electrical stimulation of RSAs. Results: Study 1: Electrical stimulation of RSAs evoked phantom touch sensations in the deafferented limb, and significantly alleviated PLP (p <  0.05). Study 2: PLP was alleviated more after electrical stimulation on RSAs compared with control electrical stimulation (p <  0.05). However, the analgesic effects of electrical stimulation on RSAs were observed only in the short term, not in the long term (p >  0.05). Conclusions: Electrical stimulation of RSAs not only evoked phantom touch sensation but also alleviated PLP in the short term. The results indicate that electrical stimulation of RSAs may provide a useful practical rehabilitation technique for PLP. Future studies will be required to clarify the mechanisms underlying immediate PLP alleviation via electrical stimulation of RSAs.

Type I adenylyl cyclase functions as a coincidence detector for control of cyclic AMP response element-mediated transcription: synergistic regulation of transcription by Ca2+ and isoproterenol

1994 ◽  
Vol 14 (12) ◽  
pp. 8272-8281
Author(s):  
S Impey ◽  
G Wayman ◽  
Z Wu ◽  
D R Storm
Keyword(s):  
Cyclic Amp ◽  
Adenylyl Cyclase ◽  
Long Term Potentiation ◽  
Regulation Of Transcription ◽  
Type I ◽  
Hek 293 ◽  
293 Cells ◽  
Term Potentiation ◽  
Stimulation Of

Studies carried out with mammals and invertebrates suggest that Ca(2+)-sensitive adenylyl cyclases may be important for neuroplasticity. Long-term potentiation in the hippocampus requires increases in intracellular Ca2+ which are accompanied by elevated cyclic AMP (cAMP). Furthermore, activation of cAMP-dependent protein kinase is required for the late stage of long-term potentiation in the CA1 region of the hippocampus, which is also sensitive to inhibitors of transcription. Therefore, some forms of synaptic plasticity may require coordinate regulation of transcription by Ca2+ and cAMP. In this study, we demonstrate that the expression of type I adenylyl cyclase in HEK-293 cells allows Ca2+ to stimulate reporter gene activity mediated through the cAMP response element. Furthermore, simultaneous activation by Ca2+ and isoproterenol caused synergistic stimulation of transcription in HEK-293 cells and cultured neurons. We propose that Ca2+ and neurotransmitter stimulation of type I adenylyl cyclase may play a role in synaptic plasticity by generating optimal cAMP signals for regulation of transcription.

EFFECT OF 3′:5′-CYCLIC AMP ON NUCLEAR AND MITOCHONDRIAL RNA SYNTHESIS OF RAT ADRENOCORTICAL CELLS

1972 ◽  
Vol 70 (1) ◽  
pp. 81-88 ◽  
Author(s):  
G. G. Nussdorfer ◽  
G. Mazzocchi
Keyword(s):  
Cyclic Amp ◽  
Rna Synthesis ◽  
Mitochondrial Rna ◽  
Adrenocortical Cells ◽  
Hypophysectomized Rats ◽  
High Resolution Autoradiography ◽  
Intracellular Mediators ◽  
Stimulation Of ◽  
Trophic Action

ABSTRACT The effect of 3′:5′-cyclic AMP (cAMP) on the incorporation of 3H-uridine into adrenocortical cells of hypophysectomized rats was investigated by high resolution autoradiography. The quantitative analysis of autoradiographs shows that cAMP, like ACTH, enhances the tracer incorporation into both nuclei and mitochondria. These findings are discussed in relation to the results of various investigations, indicating that cAMP functions as an intracellular mediator of the long-term trophic action of ACTH on the adrenal cortex. It is suggested that the mechanism of this action of cAMP consists in the stimulation of both nuclear and mitochondrial RNA synthesis. Furthermore, the possibility that the trophic action of ACTH on the adrenal gland involves other intracellular mediators, as well as cAMP, is suggested.

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.

Is leucine an allosteric modulator of the lysine transporter in the intestinal basolateral membrane?

1987 ◽  
Vol 253 (5) ◽  
pp. G637-G642 ◽  
Author(s):  
K. Lawless ◽  
D. Maenz ◽  
C. Cheeseman
Keyword(s):  
Amino Acid ◽  
Basolateral Membrane ◽  
Membrane Vesicles ◽  
Transport Systems ◽  
Low Concentrations ◽  
Carrier Mediated Transport ◽  
Order Of Magnitude ◽  
Dibasic Amino Acid ◽  
Voltage Clamping ◽  
Stimulation Of

The transport of the dibasic amino acid L-lysine was investigated using basolateral membrane vesicles prepared from rat jejunal mucosal scrapings. The majority of the carrier-mediated transport was unaffected by the presence of sodium in the incubation medium, but voltage clamping of the vesicles did increase lysine uptake, indicating an associated movement of charge. Kinetic analysis of lysine influx and efflux showed the system to be symmetrical, but although the Vmax was comparable to other amino acid transport systems in this membrane, the dissociation constant for the overall reaction (KT) was an order of magnitude larger. This low affinity for lysine would explain the relatively slow rate of transport of this amino acid across the basolateral membrane. Competition experiments indicated that this system has a relatively narrow specificity carrying only lysine, arginine, ornithine, and histidine. In contrast the presence of L-leucine caused a marked stimulation of lysine efflux and influx across the vesicles. This effect was observed with leucine concentrations as low as 0.1 microM. It is concluded that although the lysine transport system in the basolateral membrane is slow in its basal state it can be rapidly turned on by the presence of L-leucine. The remarkably low concentrations required to do this suggest a possible allosteric interaction between the transporter and this neutral amino acid.

Role of cyclic AMP in the action of dopaminergic D2 receptors of some endocrine glands in rats

1987 ◽  
Vol 7 (10) ◽  
pp. 751-755 ◽  
Author(s):  
Abdulrahim Abu-Jayyab ◽  
Ezz-Eddin S. M. El-Denshary ◽  
Abdulrahman M. Ageel ◽  
Mohamed Rafik Dakkak
Keyword(s):  
Thyroid Gland ◽  
Cyclic Amp ◽  
Adrenal Cortex ◽  
D2 Receptors ◽  
Endocrine Glands ◽  
Long Term Effects ◽  
Short Term ◽  
Presence And Absence

Short-term and long-term effects of bromocriptine mesylate (10 mg/kg i.p.) on cyclic AMP contents of the liver and some endocrine glands have been investigated in the presence and absence of sulpiride (10 mg/kg i.p.). Results revealed that bromocriptine caused significant elevations in the cyclic AMP contents of the liver and reduction in its adrenocortical content. Bromocriptine effect on the adrenal cortex was antagonized by sulpiride, whereas its effect on the liver was not changed. Bromocriptine did not change the, cyclic AMP content in the thyroid gland or the ovary.

VIP stimulation of β-naphthylamidase activity in guinea-pig thyroid sections

1985 ◽  
Vol 109 (4) ◽  
pp. 505-510 ◽  
Author(s):  
P. A. Ealey ◽  
N.J. Marshall ◽  
R. P. Ekins
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Receptor Site ◽  
Dose Response Curve ◽  
Tsh Receptor ◽  
Maximal Response ◽  
Cytochemical Bioassay ◽  
Order Of Magnitude ◽  
Specific Receptors ◽  
Stimulation Of

Abstract. Subsequent to the discovery of vasoactive intestinal peptide (VIP) in the thyroid gland, VIP has been shown to stimulate various thyroid functions. The site of interaction of VIP with the thyroid follicular cell is at present not known, and this study has used the ultrasensitive cytochemical bioassay (CBA) for thyroid stimulators to investigate this further. Exposure of thyroid sections for 3 min to VIP resulted in increased naphthylamidase activity, with half-maximal response observed at 3 × 10−13 m VIP. This response to such low doses of VIP is consistent with the CBA being ultrasensitive to other thyroid stimulators e.g. TSH, thyroid stimulating antibodies and forskolin. The response to VIP was abolished by rabbit anti-VIP antiserum. The dose-response curve to VIP was bell-shaped (as with the other stimulators), maximal stimulation occurring at 10−12 m VIP. In contrast, however, to other thyroid stimulators, namely TSH, LATS-B and 3 monoclonal stimulating antibodies, whose ascending limbs of the doseresponse curves extended over 3-4 orders of magnitude, the VIP curve rose rapidly from basal to maximal tissue stimulation from 10−13 to 10−12m VIP, i.e. one order of magnitude. This unusual dose-response curve to VIP was parallel to that produced by forskolin. 11E8, a monoclonal 'blocking' antibody which is a potent inhibitor of TSH stimulation, did not 'block' forskolin stimulation, consistent with the belief that forskolin acts at a post-receptor site. However, unlike forskolin, VIP was inhibited by monoclonal 11E8, which may imply a hitherto unexpected involvement of the TSH receptor in VIP stimulation of the thyroid or, alternatively, steric inhibition by 11E8 when bound to the TSH receptor of VIP interaction with adjacent VIP-specific receptors.

Effect of lanthanum on the inotropic response of isoproterenol: role of the superficially bound calcium

1985 ◽  
Vol 63 (9) ◽  
pp. 1106-1112 ◽  
Author(s):  
Ahmad B. Fawzi ◽  
John H. McNeill
Keyword(s):  
Cyclic Amp ◽  
Positive Inotropic Effect ◽  
Direct Action ◽  
Maximum Response ◽  
Inotropic Response ◽  
Guinea Pig Heart ◽  
Low Concentrations ◽  
Stimulation Of ◽  
Calcium Pool

Mammalian myocardial contractility is believed to be related to the amount of calcium contained in a highly labile superficial calcium pool. The purpose of this study was to determine the role of such sites in the positive inotropic effect of isoproterenol. Lanthanum, an ion that is restricted to the extracellular space and that displaces the superficially bound calcium, was selected as a tool for this investigation. In Langendorff preparations of the guinea pig heart, lanthanum decreased the basal contractility index (+ dP/dtmax) in a concentration-dependent fashion (0.05–3μM) and blocked the inotropic response of isoproterenol in a noncompetitive manner (0.25–3 μM). Three-micromolar lanthanum (i) reduced basal contractility and the maximum response to isoproterenol by 97 and 95%, respectively, (ii) had no significant effect (p > 0.05) on basal and isoproterenol-induced cyclic AMP levels, and (iii) had no effect on the Kd of [3H]nitrendipine binding, but reduced the Bmax by 31%. While 1 μM lanthanum reduced basal contractility and the maximum response to isoproterenol by 90 and 70%, respectively, it had no effect on [3H]nitrendipine binding. These results suggest that the effects of such low concentrations of lanthanum (≤3 μM) are not related to a direct action on the calcium channels and are not mediated by an inhibition of isoproterenol stimulation of the enzyme adenylate cyclase. Therefore, one interpretation of these results suggests that superficially bound calcium is required for the inotropic response of isoproterenol.

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