Effect of Diphosphonates on Adenosine 3′:5′-Cyclic Monophosphate in Mouse Calvaria after Stimulation by Parathyroid Hormone in vitro

1976 ◽  
Vol 50 (6) ◽  
pp. 473-478
Author(s):  
U. Gebauer ◽  
R. G. G. Russell ◽  
M. Touabi ◽  
H. Fleisch
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Bone Cells ◽  
Essential Feature ◽  
Cyclic Monophosphate ◽  
Inhibit Bone Resorption ◽  
Mouse Calvaria

1. The diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethylene diphosphonate (Cl2MDP), inhibit bone resorption in animals and in explanted bone in tissue culture. The possibility that these effects might be due to inhibition of skeletal adenylate cyclase has been studied. 2. EHDP and Cl2MDP, added for 30 mm to the incubation medium at concentrations known to inhibit bone resorption, had no effect on basal content of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) of mouse calvaria incubated in vitro, nor did they inhibit the rise in cyclic AMP induced by bovine parathyroid hormone. 3. Pretreatment of mice for 3 days with Cl2MDP also had no effect on cyclic AMP under basal conditions or after incubation of explanted calvaria with parathyroid hormone in vitro. EHDP under similar conditions slightly inhibited the increase induced by parathyroid hormone but had no effect on basal concentrations of cyclic AMP. 4. It is suggested that the inhibition of adenylate cyclase is not an essential feature of the reduction of bone resorption by diphosphonates, which may act by direct inhibitory effects on the dissolution of hydroxyapatite and perhaps by other unidentified effects on bone cells.

scholarly journals Rainbow trout hypocalcin stimulates bone resorption in embryonic mouse calvaria in vitro in a PTH-like fashion

1989 ◽  
Vol 143 (1) ◽  
pp. 165-175
Author(s):  
F. P. Lafeber ◽  
M. P. Herrmann-Erlee ◽  
G. Flik ◽  
S. E. Wendelaar Bonga
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Tertiary Structure ◽  
Lactate Production ◽  
Dependent Manner ◽  
Embryonic Mouse ◽  
Molar Basis ◽  
Mouse Calvaria ◽  
Dose Dependent

Hypocalcin, the major hormone with hypocalcaemic action in fish, was isolated from trout corpuscles of Stannius (SCs). The bioactivity of hypocalcin was assessed in a parathyroid hormone (PTH) bioassay involving bone resorption in embryonic mouse calvaria. Calcium and phosphate release and lactate production were stimulated in a dose-dependent manner by hypocalcin. On a molar basis about equal amounts of hypocalcin and PTH were required to obtain similar effects in this assay. Hypocalcin did not stimulate cyclic AMP production either in mouse calvaria or in cultured osteoblasts. In this respect hypocalcin resembles shortened or N-terminus-modified PTH molecules that induce bone resorption without increasing cyclic AMP levels. Since hypocalcin and PTH have comparable bioactivity in this mammalian bioassay (as well as in fish bioassays), we tentatively suggest that both hormones are structurally similar and that both hormones may act via the same receptors. The two hormones show no resemblance to one another in primary structure, so we suggest that they have similarities in tertiary structure.

Establishment of a rapid bone resorption in vitro assay using previiously frozen mouse unfractionated bone cells pretreated with parathyroid hormone

Bone ◽  
1993 ◽  
Vol 14 (6) ◽  
pp. 829-834 ◽  
Author(s):  
K. Kitamura ◽  
M. Katoh ◽  
O. Komiyama ◽  
H. Kitagawa ◽  
F. Matsubara ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Cells ◽  
In Vitro Assay ◽  
Vitro Assay

scholarly journals Parathyroid hormone and prostaglandin E2 stimulate both inositol phosphates and cyclic AMP accumulation in mouse osteoblast cultures

1988 ◽  
Vol 252 (1) ◽  
pp. 263-268 ◽  
Author(s):  
R W Farndale ◽  
J R Sandy ◽  
S J Atkinson ◽  
S R Pennington ◽  
S Meghji ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Prostaglandin E2 ◽  
Intracellular Calcium ◽  
Bone Cells ◽  
Inositol Phosphates ◽  
Bone Matrix ◽  
Bone Cell ◽  
Cyclic Amp Accumulation

Parathyroid hormone (PTH) and prostaglandin E2 (PGE2) are physiological agonists which stimulate bone cells to resorb bone, a process by which the mineralized extracellular bone matrix is dissolved. Bone resorption has a key role in the maintenance of plasma calcium levels. It has been established that both PTH and PGE2 activate adenylate cyclase in osteoblasts, but it is apparent that (1) the two agents have qualitatively different effects on osteoblasts, and (2) the generation of cyclic AMP cannot account for all the effects of PTH on bone cell metabolism. Others have demonstrated that PTH and PGE2 may also elevate intracellular calcium levels, but the mechanism by which this is achieved has not been fully defined. Here we have investigated the effects of PTH on neonatal mouse osteoblasts in culture and shown that physiological concentrations of the hormone (50 nM) caused a small increase (22%) in total inositol phosphates accumulation, with a larger increase (40%) in inositol trisphosphate. We found that this activation occurred at lower concentration than was necessary to activate adenylate cyclase. PGE2 was a more effective activator of inositol phosphates accumulation than PTH, causing up to 300% increase in the total inositol phosphates after 30 min. Both PTH and PGE2 stimulated cyclic AMP accumulation, but the activation of adenylate cyclase by forskolin did not enhance inositol phosphates production. We conclude that both PTH and PGE2 stimulate phosphoinositide turnover in mouse osteoblasts and suggest that this mechanism may contribute to their elevation of intracellular calcium in bone cells.

Cytochemical Evidence for Presynatic β-Adrenergic Regulation of Secretion in the Developing Rat Submandibular Gland

1977 ◽  
Vol 35 ◽  
pp. 430-431
Author(s):  
L.S. Cutler
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Submandibular Gland ◽  
Neonatal Rat ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Parotid Glands ◽  
Adrenergic Agonist ◽  
Rat Submandibular Gland

Many studies previously have shown that the B-adrenergic agonist isoproterenol and the a-adrenergic agonist norepinephrine will stimulate secretion by the adult rat submandibular (SMG) and parotid glands. Recent data from several laboratories indicates that adrenergic agonists bind to specific receptors on the secretory cell surface and stimulate membrane associated adenylate cyclase activity which generates cyclic AMP. The production of cyclic AMP apparently initiates a cascade of events which culminates in exocytosis. During recent studies in our laboratory it was observed that the adenylate cyclase activity in plasma membrane fractions derived from the prenatal and early neonatal rat submandibular gland was retractile to stimulation by isoproterenol but was stimulated by norepinephrine. In addition, in vitro secretion studies indicated that these prenatal and neonatal glands would not secrete peroxidase in response to isoproterenol but would secrete in response to norepinephrine. In contrast to these in vitro observations, it has been shown that the injection of isoproterenol into the living newborn rat results in secretion of peroxidase by the SMG (1).

Interaction between parathyroid hormone and prostaglandin E1 on cyclic AMP metabolism in rat kidney

1980 ◽  
Vol 93 (3) ◽  
pp. 339-345 ◽  
Author(s):  
Naokazu Nagata ◽  
Yuriko Ono ◽  
Narimichi Kimura
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Rat Kidney ◽  
Prostaglandin E ◽  
Cortical Tissue ◽  
Newborn Rat ◽  
Simultaneous Addition ◽  
Renal Cortical Tissue ◽  
Subsequent Addition

Abstract. The interaction between parathyroid hormone (PTH) and prostaglandin E1 (PGE1) in influencing cyclic AMP metabolism in rat renal cortical tissue was examined. PTH and PGE1 stimulated additively the adenylate cyclase activity in the homogenate of the tissue. Both PTH and PGE1 enhanced the level of cyclic AMP in the incubated renal cortical tissue, but the effect of their simultaneous addition did not exceed the effect induced by PTH alone. Cyclic AMP accumulated in the incubation medium by stimulation by PTH was decreased by the simultaneous addition of PGE1. When the tissue was pre-incubated for 30 min with 2 to 10 μg/ml of PGE1, the magnitude of the increase of cyclic AMP caused by PTH subsequently added was lessened. However, the response to PTH of adenylate cyclase preparation obtained from the homogenate of PGE1-pre-treated tissue was not decreased. When first PTH was added to the incubating renal cortical tissue, the subsequent addition of PGE1 accelerated the decrease of cyclic AMP content in the tissue and decreased the amount of cyclic AMP released from the tissue. The interaction of PTH and PGE1 on cyclic AMP metabolism in the renal cortical tissue was in contrast to that seen in newborn rat calvaria where PGE1 and PTH acted additively in enhancing the level of cyclic AMP.

scholarly journals Interactions between adenylate cyclase and the yeast GTPase-activating protein IRA1.

1991 ◽  
Vol 11 (9) ◽  
pp. 4591-4598 ◽  
Author(s):  
M R Mitts ◽  
J Bradshaw-Rouse ◽  
W Heideman
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Adenylate Cyclase System ◽  
Gtpase Activating Protein ◽  
Yeast Saccharomyces Cerevisiae ◽  
Strong Candidate ◽  
Sepharose 4B ◽  
Stimulation Of ◽  
Cyclic Amp Synthesis

The adenylate cyclase system of the yeast Saccharomyces cerevisiae contains many proteins, including the CYR1 polypeptide, which is responsible for catalyzing the formation of cyclic AMP from ATP, RAS1 and RAS2 polypeptides, which mediate stimulation of cyclic AMP synthesis by guanine nucleotides, and the yeast GTPase-activating protein analog IRA1. We have previously reported that adenylate cyclase is only peripherally bound to the yeast membrane. We have concluded that IRA1 is a strong candidate for a protein involved in anchoring adenylate cyclase to the membrane. We base this conclusion on the following criteria: (i) a disruption of the IRA1 gene produced a mutant with very low membrane-associated levels of adenylate cyclase activity, (ii) membranes made from these mutants were incapable of binding adenylate cyclase in vitro, (iii) IRA1 antibodies inhibit binding of adenylate cyclase to the membrane, and (iv) IRA1 and adenylate cyclase comigrate on Sepharose 4B.

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