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Biomedical subjects

G A Rodan

Publications and source records attributed to G A Rodan.

At least 199 records · Page 11Linked to original sources
PubMed1978

Parathyroid hormone stimulation of adenylate cyclase activity and lactic acid accumulation in calvaria of osteopetrotic (ia) rats.

We have examined the effect of parathyroid hormone (PTH) on the adenylate cyclase activity of newborn osteopetrotic rat calvaria, to study a possible molecular basis for the reduced response of this mutant to PTH. Phenotypically normal littermates served as controls. We also measured the effect of PTH on kidney adenylate cyclase activity and on lactic acid accumulation in short term cultures of calvaria. PTH stimulated calvarial adenylate cyclase activity in a dose-dependent manner in both mutant rats and normal littermates. Lactic acid production was also enhanced by PTH, and no significant difference between mutants and normal littermates was observed. These findings indicate that the reduced response of the young osteopetrotic rats to PTH is not due to an absence of PTH receptors coupled to adenylate cyclase.

Adenylyl Cyclases↗
PubMed1977

Membrane changes during cartilage maturation. Increase in 5'-nucleotidase and decrease in adenosine inhibition of adenylate cyclase.

To examine the potential participation of the plasma membrane in differentiation, we studied the enzymatic activities of 5'-nucleotidase and adenylate cyclase as a function of chondrocyte maturation. 16-day-old chick embryo tibiae epiphyses were dissected into proliferative, growing and hypertrophying zones. Partially purified membrane fractions prepared by differential centrifugation from the respective tissue segments were assayed for enzymatic activity. Cell suspensions from the same segments were examined cytochemically for the presence of 5'-nucleotidase. The findings show that the 5'-nucleotidase activity of the chick embryo epiphyseal cartilage has the following characteristics: (a) it has a Km of about 25 muM for 5'AMP, and is inhibited by a mixture of 2' and 3'AMP (apparent Ki about 10(-4) M) and by AOPCP; (b) it is predominantly localized at the cell surface but is also detected in the cytoplasm and in association with nuclear heterochromatin; and (c) it increases 10-fold (on a DNA basis) during the maturation of the epiphyseal cartilage cells. The adenylate cyclase activity has these characteristics: (a) it does not change during chondrocyte maturation (on a DNA basis); (b) its susceptibility to adenosine inhibition decreases at least 10-fold. The implication of these findings relative to a possible role of adenosine in cellular communication is discussed.

Adenosine↗
PubMed1977

Evidence for preferential effects of parathyroid hormone, calcitonin and adenosine on bone and periosteum.

In order to explore the distribution of hormone-responsive cells in skeletal tissues, we have examined the effects of synthetic bovine parathyroid hormone N-terminal peptide (bPTH 1-34) and salmon calcitonin (sCT) on cyclic AMP levels in periosteum-free rat calvaria, segments of periosteum, and in isolated cells dispersed from each tissue by collagenase digestion. Synthetic bovine PTH increased cyclic AMP levels to a greater degree in calvaria and in isolated bone cells than in the periosteal segments and cells, whereas sCT was more effective in the periosteal than in the bone systems. Primary cultures prepared from bone and periosteal cell populations exhibited progressive increases in their responsiveness to bPTH (1-34) and progressive decreases in responsiveness to sCT. After six days in the culture, bone cells failed to respond to sCT, and sCT did not modify their response simultaneously added bPTH (1-34). Six-day periosteal cell cultures exhibited residual sCT responsivity and an additive response upon simultaneous exposure to high concentrations of bPTH (1-34) and sCT suggesting separate sites of hormone action. Adenosine, a known stimulator of bone cell adenylyl cyclase, caused a greater increase in periosteal cell than in bone cell cyclic AMP. bPTH (1-34)-responsive cells which enrich periosteum-free bone may be osteoblasts, in view of their histological prominence in this tissue and in the bone cell isolates. Periosteal cells which responded to sCT and to adenosine preferentially are unidentified. Although periosteal segments contained numerous fibroblast-like cells, skin fibroblasts cultured from the same fetuses were sCT-insensitive. Growth in primary culture appears to alter the number of hormone-responsive cells or responsiveness of existing cells to each hormone, or both.

Adenosine↗
PubMed1977

Epiphyseal cartilage cAMP changes produced by electrical and mechanical perturbations.

Epiphyseal cartilage from chick embryo was subjected in vitro for one to 15 minutes to static compressive forces or oscillating electric fields. The same stimuli were applied to suspensions of cells isolated from the epiphyses. At the end of the perturbation cAMP was measured in the tissue or cell extracts by radioimmunoassay. It was found that a physiological (60 g/cm2) static pressure reduced the cAMP content in the tissue and the separated cells. An oscillating electric field above 900 V/1.5 cm, 5Hz, enhanced the cAMP accumulation in the intact tissue. This effect was produced only when the long axis of the bones was oriented parallel to the electric field. In isolated cells an electric field above 750 V/1.5 cm, 5Hz, caused a decrease in cAMP content. Charged matrix macromolecules and orientation of the cells within the cell matrix may have a modulating effect on the initiation of this response. It is postulated that the change in cAMP is the early cellular signal in the response to an electrical or mechanical perturbation which leads to bone remodeling.

Animals↗
PubMed1976

Demonstration of adenylate cyclase activity in human red blood cell ghosts.

The presence of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing) EC 4.6.1.1) activity was demonstrated in human erythrocyte ghosts and was found to be around 3 pmol adenosine 3',5'-monophosphate (cyclic AMP) - 2 h-1 - mg-1 protein. This enzymatic activity is strongly stimulated by NaF and 5'-guanylimidodiphosphate, is slightly stimulated by epinephrine, norepinephrine, isoproterenol, and prostaglandin E1 and is inhibited by calcium. The hormone stimulation is not potentiated by 5'-guanylylimidodiphosphate.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

The role of calcium in the inhibition of cAMP accumulation in epiphyseal cartilage cells exposed to physiological pressure.

A hydrostatic pressure of 60g/cm sq (0.85 psi) inhibits the accumulation of cAMP in cells isolated from the proliferative zone of chick-tibia epiphyseal cartilage. The following findings indicate that this effect is mediated by a translocation of calcium: (i) the pressure enhances the cellular uptake of radiocalcium; (ii) the pressure effect on cAMP can be simulated by the calcium-ionophore A23187; (iii) the effects of pressure and A23187 are non-additive; (iv) the pressure effect is not produced in the presence of ethylenebis-(oxyethylenenitrilo)-pressure effect is not produced in the presence of ethylenebis-(oxyethylenenitrilo)-tetraacetic-acid (EGTA); (v) the particulate adenyl cyclase activity of the proliferative zone is susceptible to non-competitive calcium inhibition. Throughout this study cells from the hypertrophic zone of the same epiphyses were used as controls. In these cells the calcium uptake was enhanced by pressure, but the cAMP level was not affected by pressure, A23187 or EGTA. This change in responsiveness, which accompanies the maturation of the cartilage cells, was shown to be due to a decrease in the calcium-inhibition of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1976

Interrelationships between Ca2+ and adenylate and guanylate cyclases in the control of platelet secretion and aggregation.

Ca2+ is a powerful inhibitor (Ki is congruent to 16 muM) of basal and prostaglandin E1 (PGE1)-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity in membranes obtained from homogenized human platelets. Ca2+ (but not the ionophore A23,187) decreased V(max) of the reaction without an effect on the Ks for ATP. Neither ATP nor PGE1 affected Ki for Ca2+. In intact platelets A23,187 induced Ca2+ influx and markedly inhibited PGE1-stimulated rise in adenosine 3':5'-cyclic monophosphate (cAMP) levels. Guanylate cyclase [GTP pyrophosphate-lyase (cyclizing); EC 4.6.1.2] activity was mainly found in the soluble fraction (greater than 90%). Both soluble and membrane bound enzymes were stimulated by Mn2+ and Ca2+ and inhibited by Zn2+. Adenylate and guanylate cyclase activity were both present in a membrane fraction cyclase activity were both present in a membrane fraction which contained Ca2+ activated ATPase activity, and accumulated Ca2+ from the medium in the presence of ATP and oxalate. Other evidence indicates that these membranes originated in large part from the dense tubular system of the platelets. It is proposed that concurrent inhibition of adenylate cyclase and stimulation of guanylate cyclase facilitates the direct initiating effect of Ca2+ on platelet secretion and aggregation.

Adenosine Triphosphate↗
PubMed1975

Cyclic AMP and cyclic GMP: mediators of the mechanical effects on bone remodeling.

Compressive forces of physiological magnitude (60 grams per square centimeter) reduce the adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate content of the epiphyses of tibiae from 16-day-old chick embryos. An equivalent hydrostatic pressure applied directly to cells isolated from this tissue also affects cyclic nucleotide accumulation. The tissue response is uniform throughout the epiphysis, whereas the cell response varies according to the area of origin.

Animals↗
PubMed1975

A quantitative method for the application of compressive forces to bone in tissue culture.

A quantitative method for the application of compressive forces to long bones in culture is described. Using this method it was found that a physiological pressure of 80g/cm sq. applied to tibiae of 16-day-old chick embryos reduced glucose consumption to 50% of controls. Twenty four hours after the release of pressure glucose utilization again increased, approaching control levels. A pressure of 80 g/cm sq. also stimulated thymidine incorporation into DNA. The same pressure decreased the size of the extracellular fluid pool by 8%, but had no effect on the rate of equilibration of this pool with 22Na.

Animals↗