scholarly journals Cell cycle changes in the adenylate cyclase of C6 glioma cells.

1981 ◽  
Vol 90 (1) ◽  
pp. 169-175 ◽  
Author(s):  
R F Howard ◽  
J R Sheppard
Keyword(s):  
Cell Cycle ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Adrenergic Receptor ◽  
C6 Glioma ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Coupling Mechanism ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic

The adenylate cyclase of C6 glioma cell cultures was characterized for sensitivity to the beta-adrenergic agonist isoproterenol, as well as fluoride, and GTP as a function of the cell cycle. The mitotic phase of the cell cycle was emphasized because both the basal cellular cyclic AMP level and the intact C6 cell's capacity to accumulate cyclic AMP in response to isoproterenol decreased during mitosis. Basal and stimulated adenylate cyclase activities in mitotic cells were decreased relative to the enzyme activities in the G1, S, and G2 phases of the cell cycle. Analysis of the beta-adrenergic receptor using the radioligand(-)[3H]dihydroalprenolol showed that neither ligand affinity nor receptor density changed during the cell cycle, indicating that the reduced adenylate cyclase activity of the mitotic C6 cell was not caused by alterations in this hormone receptor. The reduction in the mitotic cell's basal adenylate cyclase activity was more prominent than the decrease in isoproterenol-, fluoride, or GTP-stimulated activities suggesting that the effectiveness of these enzymes activators (i.e., the efficiency of the coupling mechanism) was not attenuated during mitosis. These studies indicate that the intrinsic catalytic capacity (not the beta-adrenergic receptor or the coupling mechanism) of the C6 adenylate cyclase complex is reduced during mitosis and contributes to the mitotic cell's inability to accumulate and maintain the cyclic AMP concentration at the interphase level.

Adenosine receptor coupling to adenylate cyclase of rat ventricular myocyte membranes

1989 ◽  
Vol 257 (4) ◽  
pp. H1088-H1095 ◽  
Author(s):  
F. D. Romano ◽  
S. G. MacDonald ◽  
J. G. Dobson
Keyword(s):  
Adenylate Cyclase ◽  
Adenosine Receptor ◽  
Adrenergic Receptor ◽  
Receptor Agonist ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Ventricular Myocyte ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Adenosine Receptor Agonist

The effects of adenosine analogues on beta-adrenergic receptor and receptor-independent elicited increases in adenylate cyclase activity were investigated using membranes obtained from primary cultures of adult rat ventricular myocytes. Phenylisopropyladenosine, an A1-receptor agonist, at concentrations of 0.1, 1.0, and 10 microM, maximally inhibited isoproterenol-stimulated adenylate cyclase activity by 35, 55, and 41%, respectively. The inhibition by phenylisopropyladenosine was antagonized by 10 microM theophylline. One micromolar phenylisopropyladenosine was much less effective at attenuating forskolin-stimulated activity, such that the maximum inhibition was 26%. Phenylisopropyladenosine had no effect on adenylate cyclase stimulation by 5'-guanylylimidodiphosphate. Phenylaminoadenosine, an A2 agonist, at 10 microM or greater stimulated adenylate cyclase activity. This effect was not significantly inhibited by theophylline or 0.1 microM 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), which antagonized phenylisopropyladenosine inhibition of isoproterenol-stimulated adenylate cyclase activity. Additionally, N-ethylcarboxamidoadenosine, a nonselective adenosine-receptor agonist, had no effect on adenylate cyclase activity in the absence of DPCPX but stimulated adenylate cyclase activity in the presence of DPCPX. These results indicate that both A1 and A2 receptors exist on the ventricular myocyte sarcolemma. More importantly, the findings suggest that adenosine inhibition of catecholamine-stimulated adenylate cyclase activity is primarily due to an alteration in beta-adrenergic receptor-mediated transduction and perhaps in part by a direct inhibition of the catalytic component.

Developmental changes of beta-adrenergic receptor-linked adenylate cyclase of rat liver

1985 ◽  
Vol 248 (6) ◽  
pp. E712-E718 ◽  
Author(s):  
M. S. Katz ◽  
S. R. Boland ◽  
S. J. Schmidt
Keyword(s):  
Adenylate Cyclase ◽  
Rat Liver ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adrenergic Agonist ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Adrenergic Antagonist ◽  
Beta Adrenergic Agonist

beta-Adrenergic agonist-sensitive adenylate cyclase activity and binding of the beta-adrenergic antagonist(-)-[125I]iodopindolol were studied in rat liver during development of male Fischer 344 rats ages 6-60 days. In liver homogenates maximum adenylate cyclase response to beta-adrenergic agonist (10(-5) M isoproterenol or epinephrine) decreased by 73% (P less than 0.01) between 6 and 60 days, with most of the decrease (56%; P less than 0.01) occurring by 20 days. beta-adrenergic receptor density (Bmax) showed a corresponding decrease of 66% (P less than 0.01) by 20 days without subsequent change. Binding characteristics of stereospecificity, pharmacological specificity, saturability with time, and reversibility were unchanged with age. GTP-, fluoride-, forskolin-, and Mn2+-stimulated adenylate cyclase activities also decreased during development, suggesting a decrease of activity of the catalytic component and/or guanine nucleotide regulatory component of adenylate cyclase. These results indicate that the developmental decrease of beta-adrenergic agonist-sensitive adenylate cyclase activity may result from decreased numbers of beta-adrenergic receptors. Developmental alterations of nonreceptor components of the enzyme may also contribute to changes of catecholamine-sensitive adenylate cyclase.

Beta-receptors and adenylate cyclase: comparison of nonischemic, ischemic, and postmortem tissue

1990 ◽  
Vol 258 (1) ◽  
pp. H140-H144 ◽  
Author(s):  
D. E. Vatner ◽  
M. A. Young ◽  
D. R. Knight ◽  
S. F. Vatner
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Striking Similarity ◽  
Receptor Density ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic

We compared the effects of myocardial ischemia and postmortem changes on beta-adrenergic receptors and their coupling to adenylate cyclase activity. The effects of 1 h of left circumflex coronary artery occlusion were examined in eight conscious calves, which were then anesthetized with pentobarbital sodium, and the left ventricle was divided into nonischemic and ischemic regions. A crude membrane fraction was prepared from each region and from the nonischemic tissue 1 h postmortem. beta-Adrenergic receptor density increased (152 +/- 55%) and decreases in basal (-21 +/- 6.1%), isoproterenol-stimulated (-25 +/- 8.0%), 5'-guanylylimidodiphosphate [Gpp(NH)p]-stimulated (-17 +/- 5.8%), fluoride-stimulated (-26 +/- 5.8%), and forskolin-stimulated (-31 +/- 8.4%) adenylate cyclase activities were observed in the ischemic myocardium compared with nonischemic myocardium. Similarly, in postmortem samples, beta-adrenergic receptor density rose 58 +/- 16%, whereas decreases in basal (-48 +/- 8.7%), isoproterenol-stimulated (-61 +/- 7.8%), Gpp(NH)p-stimulated (-58 +/- 7.0%), fluoride-stimulated (-64 +/- 6.1%), and forskolin-stimulated (-52 +/- 6.2%) adenylate cyclase activities were observed. Agonist-binding competition curves with isoproterenol were shifted, indicating that beta-adrenergic receptors were binding agonists with low affinity in both the ischemic and postmortem myocardium. The marked, but directionally opposite, changes in receptor density and adenylate cyclase that occur postmortem indicate the importance of prompt processing of tissues. The striking similarity in response of beta-adrenergic receptor agonist and antagonist binding and adenylate cyclase activity in ischemic and postmortem tissue raises the speculation that similar mechanisms may operate under both conditions.

Glucocorticoids modulate beta-adrenoceptor subtypes and adenylate cyclase in brown fat

1988 ◽  
Vol 255 (2) ◽  
pp. E153-E158 ◽  
Author(s):  
P. J. Scarpace ◽  
L. A. Baresi ◽  
J. E. Morley
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptor ◽  
Weight Maintenance ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Receptor Subtype ◽  
Receptor Density ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Brown Adipose

Thermogenesis in brown adipose tissue (BAT) serves as a regulator of body temperature and weight maintenance. Thermogenesis can be stimulated by catecholamine activation of adenylate cyclase through the beta-adrenergic receptor. Glucocorticoids potentiate the action of catecholamines in some tissues by increasing the expression of beta-adrenergic receptors. Paradoxically, glucocorticoids suppress and adrenalectomy enhances BAT thermogenesis. To further study the reasons for this discrepancy, we assessed the effects of methylprednisolone administration, adrenalectomy, and adrenalectomy with corticosterone replacement on adenylate cyclase activity in BAT and on beta-adrenergic receptor density in lungs and BAT of rats. In lungs, the density of the beta 2-adrenergic receptor subtype increases after methylprednisolone administration and decreases after adrenalectomy. There was no change in BAT receptor density, but isoproterenol-, NaF-, and forskolin-stimulated adenylate cyclase activity was reduced by 20–35% after methylprednisolone treatment. There was a two- to threefold increase in adenylate cyclase activity after adrenalectomy, which was reversed by corticosterone administration. These data suggest that one mechanism by which glucocorticoids regulate BAT thermogenesis is by modulating the beta-adrenergic pathway at the level of adenylate cyclase activation.

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