scholarly journals Abaloparatide exhibits greater osteoanabolic response and higher cAMP stimulation and β ‐arrestin recruitment than teriparatide

2019 ◽  
Vol 7 (19) ◽  
Author(s):  
Karim Sahbani ◽  
Christopher P. Cardozo ◽  
William A. Bauman ◽  
Hesham A. Tawfeek
Keyword(s):  
Camp Stimulation

scholarly journals Functional Promiscuity of Gene Regulation by Serpentine Receptors in Dictyostelium discoideum

1998 ◽  
Vol 18 (10) ◽  
pp. 5744-5749 ◽  
Author(s):  
Irene Verkerke-Van Wijk ◽  
Ji-Yun Kim ◽  
Raymond Brandt ◽  
Peter N. Devreotes ◽  
Pauline Schaap
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Dictyostelium Discoideum ◽  
Developmental Regulation ◽  
Mutant Cell ◽  
Gene Induction ◽  
Specific Gene ◽  
Wild Type ◽  
Animal Development ◽  
Camp Stimulation

ABSTRACT Serpentine receptors such as smoothened and frizzled play important roles in cell fate determination during animal development. InDictyostelium discoideum, four serpentine cyclic AMP (cAMP) receptors (cARs) regulate expression of multiple classes of developmental genes. To understand their function, it is essential to know whether each cAR is coupled to a specific gene regulatory pathway or whether specificity results from the different developmental regulation of individual cARs. To distinguish between these possibilities, we measured gene induction in car1 car3 double mutant cell lines that express equal levels of either cAR1, cAR2, or cAR3 under a constitutive promoter. We found that all cARs efficiently mediate both aggregative gene induction by cAMP pulses and induction of postaggregative and prespore genes by persistent cAMP stimulation. Two exceptions to this functional promiscuity were observed. (i) Only cAR1 can mediate adenosine inhibition of cAMP-induced prespore gene expression, a phenomenon that was found earlier in wild-type cells. cAR1’s mediation of adenosine inhibition suggests that cAR1 normally mediates prespore gene induction. (ii) Only cAR2 allows entry into the prestalk pathway. Prestalk gene expression is induced by differentiation-inducing factor (DIF) but only after cells have been prestimulated with cAMP. We found that DIF-induced prestalk gene expression is 10 times higher in constitutive cAR2 expressors than in constitutive cAR1 or cAR3 expressors (which still have endogenous cAR2), suggesting that cAR2 mediates induction of DIF competence. Since in wild-type slugs cAR2 is expressed only in anterior cells, this could explain the so far puzzling observations that prestalk cells differentiate at the anterior region but that DIF levels are actually higher at the posterior region. After the initial induction of DIF competence, cAMP becomes a repressor of prestalk gene expression. This function can again be mediated by cAR1, cAR2, and cAR3.

scholarly journals cAMP induces a rapid and reversible modification of the chemotactic receptor in Dictyostelium discoideum.

1985 ◽  
Vol 100 (3) ◽  
pp. 715-720 ◽  
Author(s):  
C Klein ◽  
J Lubs-Haukeness ◽  
S Simons
Keyword(s):  
Dictyostelium Discoideum ◽  
Concentration Dependence ◽  
Time Course ◽  
Camp Synthesis ◽  
Sds Page ◽  
Reversible Modification ◽  
Camp Receptor ◽  
Camp Stimulation ◽  
Stimulation Of

Stimulation, within 1 min after cAMP stimulation, of aggregation-competent Dictyostelium discoideum amebae was found to cause a rapid (within 1 min) modification of the cell's surface cAMP receptor. The modified receptor migrated on SDS PAGE as a 47,000-mol-wt protein, as opposed to a 45,000-mol-wt protein labeled on unstimulated cells. The length of time this modified receptor could be detected depended upon the strength of the cAMP stimulus: 3-4 min after treatment with 10(-7) M cAMP, cells no longer possessed the 47,000-mol-wt form of the cAMP receptor. Instead, the 45,000-mol-wt form was present. Stimulation of cells with 10(-5) M cAMP, however, resulted in the persistent (over 15 min) expression of the modified receptor. The time course, concentration dependence, and specificity of stimulus for this cAMP-induced shift in the cAMP receptor were found to parallel the cAMP-stimulated phosphorylation of a 47,000-mol-wt protein. In addition, both phenomena were shown to occur in the absence of endogenous cAMP synthesis. The possibility that the cAMP receptor is phosphorylated in response to cAMP stimulation, and the role of this event in cell desensitization, are discussed.

Mechanism and control of salt absorption in locust rectum

1983 ◽  
Vol 244 (2) ◽  
pp. R131-R142 ◽  
Author(s):  
J. Hanrahan ◽  
J. E. Phillips
Keyword(s):  
Apical Membrane ◽  
Electrical Coupling ◽  
Kinetic Studies ◽  
Malpighian Tubules ◽  
General Increase ◽  
Cl Transport ◽  
Ion Sensitive Microelectrodes ◽  
And Control ◽  
K Permeability ◽  
Camp Stimulation

The rectum is the main reabsorptive site in the excretory system of locusts. The primary urine entering this organ from the Malpighian tubules is rich in K+ (140 mM) and Cl- (90 mM), and most of this fluid is normally reabsorbed. Fluid and active Cl- reabsorption in the rectum are regulated by neuropeptide hormones from the corpus cardiacum. We have studied the mechanism of KCl reabsorption using voltage clamp, tracers, double-barreled ion-sensitive microelectrodes, and ion substitutions. Locust Cl- absorption differs from vertebrate systems in that it is not dependent on Na+ or HCO-3/CO2, and it is insensitive to normal inhibitors of Cl- transport. Entry of Cl- into rectal cells is active, electrogenic, and stimulated by luminal K+. This cation substantially increases the electrochemical gradient across the apical membrane against which Cl- is pumped; therefore K+ does not act solely and indirectly by electrical coupling. Kinetic studies also suggest that K+ activates the Cl- pump. Consequently at least two levels of control are exerted during cAMP stimulation; K+ permeability of the epithelium and the transepithelial potential generated by active Cl- transport both increase. The enhanced net K+ absorption from the lumen side after stimulation is largely passive, being electrically coupled to Cl- transport. However, this general increase in KCl absorption is "fine tuned" by K+ itself, through its direct effect on the Cl- pump.

scholarly journals cAMP activates an ATP-permeable pathway in neonatal rat cardiac myocytes

2000 ◽  
Vol 279 (1) ◽  
pp. C173-C187 ◽  
Author(s):  
Alan S. Lader ◽  
Yong-Fu Xiao ◽  
Catherine R. O'Riordan ◽  
Adriana G. Prat ◽  
G. Robert Jackson ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Single Channel ◽  
Atp Release ◽  
Neonatal Rat ◽  
Luciferase Assay ◽  
Neonatal Rat Cardiac Myocytes ◽  
Single Channel Currents ◽  
Rat Cardiac Myocytes ◽  
Camp Stimulation ◽  
R Domain

The molecular mechanisms associated with intracellular ATP release by the heart are largely unknown. In this study the luciferin-luciferase assay and patch-clamp techniques were used to characterize the pathways responsible for ATP release in neonatal rat cardiac myocytes (NRCM). Spontaneous ATP release by NRCM was significantly increased after cAMP stimulation under physiological conditions. cAMP stimulation also induced an anion-selective electrodiffusional pathway that elicited linear, diphenylamine-2-carboxylate (DPC)-inhibitable Cl− currents in either symmetrical MgCl2 or NaCl. ATP, adenosine 5′- O-(3-thiotriphosphate), and the ATP derivatives ADP and AMP, permeated this pathway; however, GTP did not. The cAMP-induced ATP currents were inhibited by DPC and glibenclamide and by a monoclonal antibody raised against the R domain of the cystic fibrosis transmembrane conductance regulator (CFTR). The channel-like nature of the cAMP-induced ATP-permeable pathway was also determined by assessing protein kinase A-activated single channel Cl− and ATP currents in excised inside-out patches of NRCM. Single channel currents were inhibited by DPC and the anti-CFTR R domain antibody. Thus the data in this report demonstrate the presence of a cAMP-inducible electrodiffusional ATP transport mechanism in NRCM. Based on the pharmacology, patch-clamping data, and luminometry studies, the data are most consistent with the role of a functional CFTR as the anion channel implicated in cAMP-activated ATP transport in NRCM.

Isotonic volume reduction associated with cAMP stimulation of 36Cl efflux from jejunal crypt epithelial cells

1994 ◽  
Vol 267 (3) ◽  
pp. G387-G392 ◽  
Author(s):  
R. J. MacLeod ◽  
P. Lembessis ◽  
J. R. Hamilton
Keyword(s):  
Epithelial Cells ◽  
Cell Volume ◽  
Channel Blocker ◽  
Volume Reduction ◽  
K Channel ◽  
Sensitive Volume ◽  
Conductive Pathway ◽  
Camp Stimulation ◽  
Intestinal Crypt Cell ◽  
Crypt Cells

To determine the effect of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) on the isotonic volume of jejunal crypt epithelial cells, we isolated these cells by sequential perfusion using a hyperosmolar Ca(2+)-free solution and measured cell volume electronically. 8-BrcAMP caused rapid shrinkage to a reduced but stable cell volume; this isotonic volume reduction was prevented by either a Cl(-)-channel blocker, anthracene-9-carboxylate (A-9C), or Ba2+, a K(+)-channel blocker. 8-BrcAMP substantially increased the rate of A-9C-sensitive 36Cl efflux from crypt cells; this increased rate of efflux was not influenced by Ba2+ but was abolished by alterations in membrane potential. Following 8-BrcAMP-stimulated isotonic volume reduction, addition of either Ba2+ or A-9C caused the crypt cells to reswell. In contrast, 8-BrcAMP added to enterocytes isolated from the villus compartment did not result in A-9C-sensitive volume reduction or in an increased rate of 36Cl efflux. Our data demonstrate that epithelial cells isolated from jejunal crypt compartments respond directly to cAMP with a rapid volume reduction that is paralleled by an increase in 36Cl efflux through a conductive pathway. Unlike other Cl- secretory epithelial cells, the intestinal crypt cell does not appear to regulate its volume in an isotonic medium after cAMP-induced shrinkage.

Vasopressin- and cAMP-induced changes in ultrastructure of isolated perfused inner medullary collecting ducts

1993 ◽  
Vol 265 (2) ◽  
pp. F225-F238 ◽  
Author(s):  
S. Nielsen ◽  
J. Muller ◽  
M. A. Knepper
Keyword(s):  
Water Permeability ◽  
Apical Membrane ◽  
Endocytic Pathway ◽  
Ultrastructural Changes ◽  
Osmotic Water Permeability ◽  
Intercellular Spaces ◽  
Osmotic Water ◽  
Collecting Ducts ◽  
Induced Changes ◽  
Camp Stimulation

Studies were performed to correlate arginine vasopressin (AVP)-induced changes in epithelial ultrastructure with changes in osmotic water permeability in isolated perfused rat terminal inner medullary collecting ducts (tIMCD). The tubules were perfused in three time periods, i.e., a 40-min basal period, a 40-min period with 0.1 nM AVP in the bath, and a 60-min withdrawal period. In each phase, the osmotic water permeability (Pf) was measured, and the perfused tubules were fixed for electron microscopy. AVP caused a four- to eightfold increase in Pf and induced several ultrastructural changes as follows: increased cell height of IMCD cells, expansion of the intercellular spaces, formation of large vacuoles, and increased coated pit density in the apical plasma membrane [from 0.6 +/- 0.2 (n = 6) to 2.9 +/- 0.3 (n = 7) pits/100 microns membrane length]. During AVP withdrawal, Pf decreased toward the basal value in association with partial reversal of the ultrastructural changes including a decrease in coated pit density to 1.0 +/- 0.2 (n = 4). Stimulation with 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) (0.1 mM) produced similar changes in Pf. Coated pit density increased to 2.1 +/- 0.4 (n = 4) after cAMP stimulation and after cAMP withdrawal decreased to 1.2 +/- 0.2 (n = 6). In contrast to stimulation with AVP, cAMP stimulation did not result in dilated intercellular spaces or formation of large vacuoles. The only ultrastructural feature that directly correlated with the water permeability was the density of coated pits in the apical membrane. Organelles involved in the endocytic pathway were studied with cationized ferritin or albumin-gold in the luminal perfusate. At the end of 40 min basal perfusion or AVP stimulation, luminal tracer was found almost exclusively in large multivesicular bodies (MVB). Tubules perfused with tracer during AVP withdrawal demonstrated rapid tracer accumulation in small vesicles and small MVB within 3-5 min, a time point corresponding to the rapid phase of Pf decrease. Later (30-60 min) the label was mainly confined to large MVB. Occasionally during AVP stimulation or withdrawal, small coated vesicles and smooth vesicles with coated extensions were noted to contain tracer. The data demonstrate AVP-mediated coated pit formation and cellular changes and show very rapid internalization of apical membrane after AVP withdrawal.

A model eliciting transient responses

1984 ◽  
Vol 246 (1) ◽  
pp. R114-R121 ◽  
Author(s):  
E. B. Ekblad ◽  
V. Licko
Keyword(s):  
Gastric Mucosa ◽  
Adenylate Cyclase ◽  
Chemical Transformation ◽  
Transient Response ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Transient Responses ◽  
Histamine Secretion ◽  
Cyclic Monophosphate ◽  
Camp Stimulation

A simple parametrically controlled chemical transformation scheme is used to exemplify a model with transient response to sustained stimulation. More complicated schemes are also discussed. Analyses of three experimental examples are given: short-circuit current changes in toad bladder exposed to adenosine 3',5'-cyclic monophosphate (cAMP) stimulation; histamine secretion in acetylcholine-stimulated frog gastric mucosa; and cAMP dynamics, expressed in terms of adenylate cyclase dynamics, in histamine-stimulated frog gastric mucosa. The model responds primarily to the changes of the stimulator level, although it is not a model with derivative control.

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