The role of zinc status in altered cardiac adenylate cyclase activity in diabetic rats

1988 ◽  
Vol 119 (2) ◽  
pp. 174-180 ◽  
Author(s):  
Arshag D. Mooradian ◽  
John E. Morley ◽  
Philip J. Scarpace
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptor ◽  
Diabetic Rats ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Zinc Status ◽  
Dietary Zinc ◽  
Zinc Intake ◽  
Diabetic State ◽  
High Zinc

Abstract. Zinc deficiency and altered myocardial adenylate cyclase activity commonly occur in diabetes. To determine whether the zinc intake of the animal can account for the altered β-adrenergic receptor activity in the diabetic heart, we determined the β-adrenergic receptor number and isoproterenol-, NaF- and forskolin-stimulated adenylate cyclase activity in diabetic and control rats maintained on low, normal and high zinc diets for 3 weeks. Scatchard analysis of [125I]iodocyanopindolol binding to control heart membrane preparations revealed a binding capacity of 17.3 ± 1.3 fmol/mg protein with a Kd of 35 ± 1.0 pmol/l. Neither the diabetic state nor the zinc status altered these binding parameters. The isoproterenol-stimulated adenylate cyclase acticity was significantly lower in diabetic rats on low zinc diets compared with controls. The NaF- (65.1 ± 5.4 vs 60.8 ± 6.4 pmol cAMP·mg protein−1·min−1) and forskolin-stimulated adenylate cyclase activities (161 ± 9.3 vs 154 ± 21.2 pmol cAMP·mg protein−1· min−1) were not significantly altered in diabetic rats. Low dietary zinc intake compared with high zinc diet significantly increased NaF- and forskolin-stimulated adenylate cyclase activity both in diabetic rats and controls. The effect of dietary zinc content on isoproterenol-stimulated adenylate cyclase was significant in control rats only. Thus zinc intake appears to be an important determinant of cardiac adenylate cyclase activity level. Additional factors peculiar to the diabetic state are involved in the modulation of β-adrenergic responsiveness of the diabetic heart.

Regulation by progesterone of the high-affinity state of myometrial β-adrenergic receptor and of adenylate cyclase activity in the pregnant rat

1991 ◽  
Vol 6 (2) ◽  
pp. 137-145 ◽  
Author(s):  
J. Cohen-Tannoudji ◽  
V. Vivat ◽  
J. Heilmann ◽  
C. Legrand ◽  
J. P. Maltier
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Maximum Velocity ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Pregnant Rat ◽  
High Affinity ◽  
Β Adrenergic Receptors

ABSTRACT The effects of pregnancy or progesterone dominance on the β-adrenergic responsiveness of the uterus were studied in myometrial membranes from mid-and late-pregnant rats (day 15 and on the 16th h of day 22 of pregnancy respectively) or 24 h after administration of progesterone. Levels of the high (RH)- and low (RL)-affinity states of the β-adrenergic receptor were determined by competition experiments between 125I-labelled cyanopindolol binding and the selective β-agonist isoproterenol. The ratio KL/KH (respective dissociation constants) was determined since it also reflects the degree of formation of the high-affinity state of the β-adrenergic receptor. From day 15 to the 10th h of day 22 of pregnancy, two distinct affinity states were apparent: 80–55% RH (KH=0·31–0·21 μm) and 45–20% RL (KL=14–5 μm) with a ratio of KL/KH of 55–34. In the last 6 h before birth, β-adrenergic receptors underwent uncoupling which was paralleled by decreased responsiveness of myometrial adenylate cyclase to isoproterenol (maximum velocity (Vmax)=17±3 vs 44±3 fmol cyclic AMP/10 min per mg protein on day 15). At this stage of pregnancy, previous exposure to progesterone resulted in a 1·8-fold increase in 125I-labelled cyanopindolol-binding sites (Bmax) and the reappearance of the high-affinity state (67% RH, KH=0·19±0·04 (s.e.m.) μm, ratio KL/KH=81·1 ± 16·9). These results were reversed in the presence of the antiprogestin RU486 (100% RL, KL=24·6±4·1 μm, 41% reduction of Bmax). Moreover, after progesterone, adenylate cyclase activity was strongly stimulated by isoproterenol (Vmax=60±12 fmol cyclic AMP/10 min per mg protein vs 17±3 in controls). The data suggest (1) that progesterone may exert a permissive effect on β-adrenergic responsiveness of the pregnant rat myometrium and (2) that at term, both a desensitization mechanism involving uncoupling of β-adrenergic receptors and a decrease in activation of adenylate cyclase lead to a loss of myometrial response to β-agonists.

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.

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.

beta-Adrenergic receptors in the developing rabbit lung

1981 ◽  
Vol 240 (4) ◽  
pp. E351-E357 ◽  
Author(s):  
J. A. Whitsett ◽  
M. A. Manton ◽  
C. Darovec-Beckerman ◽  
K. G. Adams ◽  
J. J. Moore
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Receptor Subtypes ◽  
Beta Adrenergic Receptors ◽  
Rabbit Lung ◽  
Beta Adrenergic ◽  
Beta 2

beta-Adrenergic receptors and catecholamine-sensitive adenylate cyclase were identified and partially characterized in membrane fractions of rabbit lungs from day 25 of gestation to adulthood with the beta-adrenergic antagonists (--)-[3H]dihydroalprenolol [(--)-[3H]DHA] and (--)-[125I]iodohydroxybenzylpindolol [(--)-[125I]HYP]. beta-Adrenergic receptor number (Bmax) increased 11.5-fold during this time period, increasing progressively during the latter days of gestation and the early neonatal period, from 37 +/- 10 fmol/mg protein at 25 days gestation to 425 +/- 51 fmol/mg in the adult rabbit lung (mean +/- SD). Receptor affinity for (--)-[3H]DHA (KD = 1.8 nM) or (--)-[125I]HYP (KD - 0.104 nM) and the proportion of beta 1- and beta 2-adrenergic receptor subtypes (60% beta 1 and 40% beta 2) did not change with advancing age. Basal adenylate cyclase activity in lung homogenates decreased significantly with increasing age, whereas the activity in the presence of catecholamine or NaF remained nearly constant. Catecholamines stimulated adenylate cyclase activity at all ages studied supporting a role of the maturation of beta-adrenergic receptors in the regulation of pulmonary function.

Selective Alteration of Secretin-Stimulated Cardiac Adenylate Cyclase Activity in Streptozotocin-Diabetic Rats

1983 ◽  
Vol 15 (12) ◽  
pp. 620-622 ◽  
Author(s):  
P. Chatelain ◽  
L. Gillet ◽  
M. Waelbroeck ◽  
J. Camus ◽  
P. Robberecht ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Diabetic Rats ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Streptozotocin Diabetic Rats
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