EVIDENCE FOR A SEPARATE ADENYLATE CYCLASE SYSTEM RESPONSIVE TO BETA-ADRENERGIC STIMULATION IN THE RENAL CORTEX OF THE RAT

1974 ◽  
Vol 77 (3) ◽  
pp. 604-611 ◽  
Author(s):  
Norman H. Bell ◽  
John Fleming ◽  
Joanne Benedict ◽  
Lisa Pantzer
Keyword(s):  
Parathyroid Hormone ◽  
Adenylate Cyclase ◽  
Renal Cortex ◽  
Blocking Agent ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Increased Activity

ABSTRACT Previous studies in other laboratories had indicated that some of the effects of parathyroid hormone on skeletal tissue and the renal tubule to influence ion metabolism can be produced by beta-adrenergic stimulation. Studies were carried out to determine whether the same adenylate cyclase system in rat renal cortex is activated by parathyroid hormone and isoproterenol. At maximal effective concentration of dose response, parathyroid hormone (2 × −5 m) increased adenylate cyclase activity by some 415 per cent, isoproterenol (10−6 m) increased activity by some 40 to 50 per cent, vasopressin (10−5 m) increased activity by some 96 per cent and porcine calcitonin (10−5 m) increased activity by some 92 per cent. Dl-propranolol (10−5 m), a beta-adrenergic receptor blocking agent, prevented the increase in enzyme activity produced by isoproterenol (10−6 m), did not diminish the increase in activity produced by parathyroid hormone (10−6 m) and did not influence basal adenylate cyclase activity by itself. The combined maximal concentrations of isoproterenol together with either parathyroid hormone, vasopressin or porcine calcitonin were additive. These results indicate that there is an adenylate cyclase system in rat renal cortex which can be activated by beta-adrenergic stimulation with isoproterenol, and is separate from the systems responsive to parathyroid hormone, vasopressin or calcitonin.

Selective inhibition by epinephrine of parathyroid hormone-stimulated adenylate cyclase in rat renal cortex

1982 ◽  
Vol 242 (6) ◽  
pp. F721-F726 ◽  
Author(s):  
E. A. Woodcock ◽  
C. I. Johnston
Keyword(s):  
Parathyroid Hormone ◽  
Adenylate Cyclase ◽  
Renal Cortex ◽  
Selective Inhibition ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Renal Tubules ◽  
Direct Inhibition ◽  
Basal Activity ◽  
Absolute Decrease

Parathyroid hormone- (PTH) stimulated adenylate cyclase activity in homogenates of rat renal cortex was inhibited by l-epinephrine. The specificity of the inhibition indicated that it was mediated by alpha 2-receptors. The inhibition of PTH-stimulated activity was greater than the inhibition of basal activity. The absolute decrease in adenylate cyclase activity produced by 10-4 M l-epinephrine was from 16.3 +/-0.6 (SE) to 11.2 +/- 0.6 pmol.min-1.mg-1 for activity stimulated by 10 microgram/ml PTH. Basal activity was decreased from 2.3 +/- 0.07 to 1.7 +/- 0.04. A similar inhibition of PTH-stimulated adenylate cyclase by l-epinephrine was demonstrated in preparations of renal cortical tubules. In contrast, the quantitative decrease in vasopressin-or calcitonin-stimulated activity by 10-4 M l-epinephrine was the same as the decrease in basal activity. These results demonstrate that PTH receptors that stimulated adenylate cyclase and alpha 2-adrenergic receptors that inhibit adenylate cyclase are present on the same cells in the renal tubules. Thus, a mechanism exists whereby alpha-adrenergic agonists can oppose the tubular actions of PTH via a direct inhibition of adenylate cyclase activity.

Plasmin: A possible physiological modulator of the human platelet adenylate cyclase system

1987 ◽  
Vol 72 (4) ◽  
pp. 467-473 ◽  
Author(s):  
Serge Adnot ◽  
Nicolas Ferry ◽  
Jacques Hanoune ◽  
Marie-Use Lacombe
Keyword(s):  
Platelet Aggregation ◽  
Adenylate Cyclase ◽  
Human Platelet ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Inhibition Of Platelet Aggregation ◽  
Increased Activity

1. Plasmin was recently reported to inhibit platelet aggregation [1]. We report here on the interaction of plasmin with the adenylate cyclase system of human platelets. Human plasmin caused a dose-and time-dependent increase in adenylate cyclase activity when added to a crude platelet membrane preparation. Both basal and prostaglandin E1-stimulated adenylate cyclase activity doubled in presence of plasmin. This stimulatory activity was shared by papain and α-chymotrypsin, but not by thrombin which displayed a slightly inhibitory effect. 2. Plasmin not only stimulated platelet adenylate cyclase activity, but also suppressed the GTP-dependent α2-adrenergic inhibition, thereby producing a five- to six-fold increased activity measured in the presence of adrenaline and GTP. 3. These effects of plasmin on the adenylate cyclase system were suppressed by the addition of the protease inhibitor leupeptin, and of soybean trypsin inhibitor, indicating that proteolysis mediated these effects. 4. We also examined the adenylate cyclase activity in membranes prepared from intact platelets incubated with increasing doses of plasmin. Incubation of platelets with plasmin concentrations as low as 0.25 mg/ml resulted in an irreversible increase in membrane adenylate cyclase activity and suppression of the adrenaline-mediated inhibition of enzyme activity. 5. These results suggest that the proteolytic stimulating effect of plasmin on the platelet adenylate cyclase system may account for the inhibition of platelet aggregation.

scholarly journals Differential effects of fluoride on adenylate cyclase activity and guanine nucleotide regulation of agonist high-affinity receptor binding

1988 ◽  
Vol 254 (1) ◽  
pp. 15-20 ◽  
Author(s):  
J M Stadel ◽  
S T Crooke
Keyword(s):  
Adenylate Cyclase ◽  
Plasma Membranes ◽  
Regulatory Protein ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Guanine Nucleotide ◽  
Beta Adrenergic ◽  
High Affinity ◽  
Platelet Membranes

Fluoride ion, presumably an Al3+-F- complex, has been proposed to activate the guanine nucleotide regulatory protein (G-protein) of the visual system, transducin, by associating with GDP at the nucleotide-binding site and thus mimicking the effects of non-hydrolysable GTP analogues [Bigay, Deterre, Pfister & Chabre (1985) FEBS Lett. 191, 181-85]. We have examined this proposed model by using the adenylate cyclase complexes of frog erythrocytes, S49 lymphoma cells and human platelets. Preincubation of plasma membranes from frog erythrocytes and S49 cells with 20 mM-fluoride for 20 min at 30 degrees C strongly stimulated adenylate cyclase activity. In contrast, the preactivated membranes were still able to bind beta-adrenergic agonist with high affinity, as determined by radioligand-binding techniques. Moreover, high-affinity agonist binding in fluoride-treated membranes was fully sensitive to guanine nucleotide, which decreased beta-adrenergic-receptor affinity for agonist. Very similar results were obtained for [3H]prostaglandin E1 binding to S49 membranes pretreated with fluoride. Incubation of human platelet membranes with increasing concentrations of fluoride (1-50 mM) resulted in biphasic regulation of adenylate cyclase activity, with inhibition observed at concentrations greater than 10 mM. Preincubation of platelet membranes with 20 mM-fluoride did not affect agonist high-affinity binding to alpha 2-adrenergic receptors, nor receptor regulation by guanine nucleotide. These results suggest that the model developed from the study of transducin may not be generally applicable to the G-proteins of the adenylate cyclase system.

scholarly journals Regulation of cardiac adenylate cyclase activity in rodent models of obesity

1992 ◽  
Vol 283 (1) ◽  
pp. 203-208 ◽  
Author(s):  
D Strassheim ◽  
M D Houslay ◽  
G Milligan
Keyword(s):  
Adenylate Cyclase ◽  
Heart Tissue ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Adrenergic Stimulation ◽  
Guanine Nucleotide Binding Protein ◽  
Beta Adrenergic ◽  
Obese Zucker Rat

We have investigated beta-adrenergic regulation of adenylate cyclase activity in heart tissue membranes from the genetically obese Zucker rat, the genetically obese CBA mouse and the genetically obese diabetic (db/db) mouse. Responsiveness to beta-adrenergic stimulation was impaired in membranes from the obese Zucker rat, but not in the other models. The membranes from obese Zucker rats showed both decreased beta-adrenergic-receptor number and altered coupling between beta-adrenergic receptors and the stimulatory guanine-nucleotide-binding protein, Gs. In contrast, no alterations in either the levels of Gs or the functional interaction between this protein and the catalytic moiety of adenylate cyclase were observed. In these three genetic models of obesity we observe dissimilar alterations in the control of adenylate cyclase.

Multiple effects of phorbol esters on hormone-sensitive adenylate cyclase activity in S49 lymphoma cells

1987 ◽  
Vol 252 (6) ◽  
pp. E783-E789
Author(s):  
J. D. Bell ◽  
L. L. Brunton
Keyword(s):  
Catalytic Activity ◽  
Adenylate Cyclase ◽  
Phorbol Esters ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adrenergic Stimulation ◽  
Lymphoma Cells ◽  
Beta Adrenergic ◽  
Agonist Affinity ◽  
Hormone Sensitive

In S49 lymphoma cells, 12-O-tetradecanoyl phorbol-13-acetate (TPA) enhances adenylate cyclase activity and doubles cAMP accumulation in response to beta-adrenergic stimulation at 37 degrees C, putatively via the action of protein kinase C. At 27 degrees C, TPA has the opposite effect, inhibiting cAMP production in response to isoproterenol by approximately 25%. TPA also inhibits the response to prostaglandin E1 (PGE1), another stimulant of hormone-sensitive adenylate cyclase in these cells, by 30% at 37 degrees C and almost 50% at 27 degrees C. In contrast, TPA enhances responses to forskolin and cholera toxin at both 27 and 37 degrees C. In membranes from cells treated with TPA, PGE1-stimulated adenylate cyclase activity is inhibited by 50%, whereas the catalytic activity stimulated by NaF or forskolin is enhanced. TPA reduces the potency of both PGE1 and isoproterenol for cAMP generation by 50%. TPA causes a similar decrease in beta-adrenergic agonist affinity with no reduction in the density of either antagonist or agonist binding sites in wild type cells and in cells lacking the alpha-subunit of the stimulatory transducer protein (Gs) (cyc-) or lacking functional receptor Gs coupling (UNC). Therefore, TPA has at least three functionally distinct effects on hormone-sensitive adenylate cyclase in S49 cells: a 50% reduction in agonist affinity, attenuation of receptor-transducer coupling, and enhancement of GTP-dependent catalytic activity. We conclude that multiple and opposing effects of TPA on hormone-sensitive adenylate cyclase occur simultaneously within the same cell, affecting the responses to several agonists differently.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of oestrogen on adenylate cyclase system and glucose output in rat liver

1989 ◽  
Vol 257 (2) ◽  
pp. 407-411 ◽  
Author(s):  
S Shima ◽  
N Okeyama ◽  
N Akamatu
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Male Rats ◽  
Adenylate Cyclase System ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Oestrogen Treatment ◽  
Glucose Output

Effects of chronic oestrogen treatment on catecholamine- and glucagon-sensitive adenylate cyclase activity and glucose output in hepatocytes of castrated male rats were studied. In hepatocytes from male intact or castrated rats, the beta-adrenergic agonist isoprenaline did not stimulate adenylate cyclase activity and glycogenolysis, but glucagon markedly stimulated all these activities. Treatment of castrated animals with 17 beta-oestradiol for 7 days led to the appearance of beta-adrenergic-stimulated increases in both cyclic AMP generation and glucose output. The basal, glucagon- or fluoride-stimulated activities of adenylate cyclase of hepatic membranes prepared from oestrogen-treated rats were similar to those of control animals. Treatment with oestrogen did not influence the number or affinity of beta-adrenergic receptors. In hepatic plasma membranes from control rats, GTP failed to decrease the affinity of beta-adrenergic receptors for agonists, whereas the GTP-induced shift was apparently observed in those from oestrogen-treated animals. These results suggest that oestrogen is able to facilitate the coupling of hepatic beta-adrenergic receptors to the enzyme by increasing the effectiveness of receptor-guanine nucleotide regulation.

Adenylate cyclase agonist properties of CGP-12177A in brown fat: evidence for atypical beta-adrenergic receptors

1991 ◽  
Vol 260 (2) ◽  
pp. E226-E231
Author(s):  
P. J. Scarpace ◽  
M. Matheny
Keyword(s):  
Adenylate Cyclase ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Dependent Manner ◽  
Beta Adrenergic ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Dose Dependent ◽  
Binding Curves

Thermogenesis in brown adipose tissue (BAT) is stimulated by catecholamine activation of adenylate cyclase through the beta-adrenergic receptor. Recently it was reported that the beta-adrenergic antagonist CGP-12177A stimulates oxygen consumption in BAT. To investigate the mechanism of action of CGP-12177A in BAT, we assessed the inhibitory and stimulatory affects of CGP-12177A on the adenylate cyclase system in myocardial and BAT membranes from rats. CGP-1277A inhibited isoproterenol-stimulated adenylate cyclase activity in a dose-dependent manner, with an inhibitory constant (Ki) of 1.94 +/- 0.18 microM in BAT and 0.49 +/- 0.11 microM in the heart. However, in the absence of isoproterenol, CGP-12177A stimulated adenylate cyclase in BAT with two components of activation, and half-maximal stimulation occurred at 1 microM and 1.5 mM. In contrast, CGP-12177A did not stimulate adenylate cyclase activity in heart membranes. Propranolol inhibited the isoproterenol-stimulated activity with a potency that was one log less in BAT compared with heart. Propranolol fully blocked the high-affinity component but only weakly blocked the low-affinity component of CGP-12177A-stimulated activity in BAT. Pindolol was also less potent in BAT but inhibited the CGP-12177A-stimulated activity in a manner similar to the inhibition of the isoproterenol-stimulated activity, suggesting the CGP-12177A activation was beta-receptor mediated. Binding curves of [125I]iodocyanopindolol ([125I]ICYP) in competition with CGP-12177A demonstrated a shift to lower affinity in the presence of beta,gamma-imidoguanosine 5'-triphosphate, indicating that CGP-12177A has agonist properties with respect to the [125I]ICYP binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of benzyl alcohol on PTH receptor-adenylate cyclase system of canine kidney

1985 ◽  
Vol 248 (1) ◽  
pp. E31-E35
Author(s):  
K. J. Martin ◽  
C. L. McConkey ◽  
T. J. Stokes
Keyword(s):  
Enzyme Activity ◽  
Adenylate Cyclase ◽  
Benzyl Alcohol ◽  
Membrane Fluidity ◽  
Phospholipid Composition ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Hormone Sensitive ◽  
Canine Kidney

In many systems, perturbations of membrane architecture by changes of lipid and phospholipid composition have been shown to alter the activity of membrane-bound enzymes. The present studies examined the effect of benzyl alcohol, an agent that has been shown to increase membrane fluidity, on the parathyroid hormone (PTH)-sensitive adenylate cyclase system of canine kidney. Benzyl alcohol progressively increased basal adenylate cyclase activity up to fourfold and maximal enzyme activity in the presence of PTH, GTP, guanylimidodiphosphate, and sodium fluoride by four- to sixfold. In the presence of 20 mM Mn2+ (no Mg2+), conditions under which enzyme activity is devoid of influence of guanine nucleotides or hormones, benzyl alcohol was without effect. PTH binding was increased by 25% in the presence of benzyl alcohol without a change in binding affinity. Fluorescent polarization studies using diphenylhexatriene showed a decrease in fluorescence anisotropy in the presence of benzyl alcohol. The results suggest that benzyl alcohol facilitates the interaction of the components of the adenylate cyclase system, presumably by increasing membrane fluidity. Alterations of membrane fluidity may be a potent means of regulating hormone sensitive adenylate cyclase activity.

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