Effect of age and posture on human lymphocyte adenylate cyclase activity

1988 ◽  
Vol 74 (3) ◽  
pp. 331-334 ◽  
Author(s):  
Scott L. Mader ◽  
Alan S. Robbins ◽  
Laurence Z. Rubenstein ◽  
Michael L. Tuck ◽  
Philip J. Scarpace
Keyword(s):  
Adenylate Cyclase ◽  
Acute Stress ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Elderly Subjects ◽  
Upright Posture ◽  
Adenylate Cyclase System ◽  
Healthy Elderly ◽  
Age Related ◽  
Young Subjects

1. A number of age-related changes have been reported in the catecholamine–adrenoceptor–adenylate cyclase system. Most of the data available on these alterations come from resting subjects; the response to acute stress may provide additional insights into the age effect on these responses. 2. We measured supine and 10 min upright plasma noradrenaline and lymphocyte adenylate cyclase activity in ten healthy elderly subjects (age 66–80 years) and seven healthy young subjects (age 27–34 years). 3. Isoprenaline stimulation of lymphocyte adenylate cyclase activity was not significantly different between supine and upright positions or between elderly and young subjects. There was a marked increase in forskolin-stimulated adenylate cyclase activity in the upright posture in both elderly and young subjects. The increment over supine levels was 70% in the elderly (P < 0.025) and 73% in the young (P < 0.05). This enhanced forskolin activity was not seen in two young subjects who became syncopal. 4. These data suggest that enhanced forskolin-stimulated adenylate cyclase activity occurs after 10 min of upright posture in both elderly and young subjects, and may be relevant to immediate blood pressure regulation. We were unable to demonstrate any age-related differences in these acute adrenergic responses.

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.

Temporal effects of cytokines on neonatal cardiac myocyte Ca2+ transients and adenylate cyclase activity

1997 ◽  
Vol 272 (4) ◽  
pp. H1937-H1944 ◽  
Author(s):  
R. J. Bick ◽  
J. P. Liao ◽  
T. W. King ◽  
A. LeMaistre ◽  
J. B. McMillin ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Cardiac Myocyte ◽  
Prolonged Exposure ◽  
Neonatal Rat ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Short Exposure ◽  
Adenylate Cyclase System ◽  
Long Term Treatment

This study investigates the hypothesis that inflammatory cytokines, interleukin (IL)-1alpha IL-1beta, and tumor necrosis factor (TNF), influence cardiac function by affecting calcium homeostasis and that this effect is mediated by the beta-adrenergic-adenylate cyclase system. After 4 days in culture, neonatal rat ventricular myocytes were treated with cytokines (10 ng/ml) for short (2 h) or longer (18 h) times. Myocyte calcium, contractility, and adenylate cyclase were measured under each condition. Anticipated stepwise increases in adenylate cyclase and intracellular calcium were found in controls (non-cytokine-treated) with 10(-7) M isoproterenol, 10(-7) M isoproterenol + 0.1 mM guanosine triphosphate, and 10(-9) M forskolin. Cells in the presence of cytokine for 2 h show increased basal calcium levels but no changes in adenylate cyclase activities, and isoproterenol fails to elevate adenylate cyclase levels or affect contractile shortening. After long-term treatment with IL-1beta or TNF, but not IL-1alpha, the significantly elevated levels of basal systolic calcium remain, and isoproterenol increases adenylate cyclase activity, unlike after short exposure. Forskolin maximally activates adenylate cyclase following both short- and long-term incubation, but the stepwise increase in activity is blunted following prolonged exposure. Thus short-term cytokine treatment blocks the adrenergic receptor-mediated increases in adenosine 3',5'-cyclic monophosphate, dissociating adenylate cyclase activation from cytokine-mediated increases in cell calcium, whereas longer treatment apparently produces direct affects on adenylate cyclase. Time-dependent differences in contractile response were found with IL-1alpha at 2 h and TNF at 18 h, implying that myofibrillar responsiveness to increased cytoplasmic calcium is dependent on both cytokine species and exposure time.

Relationship of follicle stimulating hormone (FSH)-sensitive adenylate cyclase activity to FSH binding in immature rat ovaries following administration of pregnant mare serum gonadotrophin

1982 ◽  
Vol 101 (4) ◽  
pp. 625-629 ◽  
Author(s):  
C. Y. Lee ◽  
L. E. Reichert
Keyword(s):  
Adenylate Cyclase ◽  
Dose Response ◽  
Follicle Stimulating Hormone ◽  
Optimal Dose ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Immature Rat ◽  
Pregnant Mare Serum Gonadotrophin ◽  
Stimulating Hormone

Abstract. The time and dose-response relationships of human follicle stimulating hormone (hFSH)-sensitive adenylate cyclase activity to hFSH binding was studied in the immature rat ovary following an sc injection of pregnant mare serum gonadotrophin (PMSG). When an optimal dose of PMSG (10 IU/rat) was administered, a marked increase in hFSH-sensitive activity was observed at day 2, followed by a sharp decline at day 3. This was accompanied by a parallel rise and fall in ovarian hFSH binding activity. When immature rats were given various doses (5–100 IU/rat) of PMSG for 2 days, hFSH-sensitive adenylate cyclase activity increased sharply and maximal stimulation was obtained at 10 IU/rat. A close correlation was also observed with respect to dose-response for hCG-sensitive adenylate cyclase and hCG binding activities. It is concluded that: 1) PMSG administration with an optimal dose to the immature rat induced ovarian FSH and LH-hCG receptors, and an adenylate cyclase system highly sensitive to hFSH and hCG, and 2) the acquisition and responsiveness of adenylate cylcase to gonadotrophins are closely related to the appearance and the numbers of gonadotrophin receptors.

Effect of ‘Autonomic Blockade’ on Cardiac β-Adrenergic Chronotropic Responsiveness in Healthy Young, Healthy Elderly and Endurance-Trained Elderly Subjects

1994 ◽  
Vol 87 (3) ◽  
pp. 297-302 ◽  
Author(s):  
G. A. Ford ◽  
O. F. W. James
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Geometric Mean ◽  
Cardiovascular Responses ◽  
The Elderly ◽  
Elderly Subjects ◽  
Healthy Elderly ◽  
Age Related ◽  
Autonomic Blockade ◽  
Young Subjects

1. Cardiac chronotropic responses to isoprenaline are reduced with ageing in man. It is unclear whether this is due to reduced cardiac β-adrenergic sensitivity or to age-associated differences in reflex cardiovascular responses to the vasodilatory effects of isoprenaline. Age-associated changes in physical activity are also reported to influence β-adrenergic sensitivity. 2. The aim of the present study was to determine the contribution of alterations in reflex changes in parasympathetic and sympathetic influences and physical fitness to the age-associated reduction in cardiac chronotropic responses to β-adrenergic agonists. 3. The effect of ‘autonomic blockade’ with atropine (40 μg/kg intravenously) and clonidine (4 μg/kg intravenously) on blood pressure, heart rate and chronotropic responses to intravenous bolus isoprenaline doses was determined in eight healthy young (mean age 21 years), nine healthy elderly (72 years) and 10 endurance-trained elderly (69 years) subjects. 4. Elderly subjects had a reduced increase in heart rate after atropine (young, 49 ± 9 beats/min; elderly, 36 ± 5 beats/min; endurance-trained elderly, 34 ± 12 beats/min; P < 0.01) and did not demonstrate the transient increase in systolic blood pressure after clonidine observed in young subjects (young, 11 ± 10 mmHg; elderly, −12 ± 16 mmHg; endurance-trained elderly, −18 ± 11 mmHg; P < 0.01). 5. Cardiac chronotropic sensitivity to isoprenaline after ‘autonomic blockade’ increased in the young but decreased in the elderly subjects. The isoprenaline dose that increased heart rate by 25 beats/min before and after autonomic blockade' was: young, before 1.6 μg, after 2.8 μg, P < 0.01 (geometric mean, paired test); elderly, before 6.9 μg, after 3.6 μg, P < 0.05; endurance-trained elderly, before 5.9 μg, after 4.0 μg, P < 0.05. Cardiac chronotropic sensitivity to isoprenaline was significantly reduced in elderly compared with young subjects before (P < 0.01) but was similar after (P = 0.09) ‘autonomic blockade’. Chronotropic sensitivity did not differ between healthy and endurance-trained elderly subjects before or after ‘autonomic blockade’. 6. The age-associated reduction in cardiac chronotropic responses to bolus isoprenaline is primarily due to an age-related reduction in the influence of reflex cardiovascular responses on heart rate and not to an age-related reduction in cardiac β-adrenergic sensitivity. Endurance training is not associated with altered β-adrenergic chronotropic sensitivity in the elderly. The transient pressor response to intravenously administered clonidine may be lost in ageing man.

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.

Effect of metabolic acidosis on the PTH receptor-adenylate cyclase system of canine kidney

1985 ◽  
Vol 249 (4) ◽  
pp. F566-F572
Author(s):  
E. Bellorin-Font ◽  
J. Humpierres ◽  
J. R. Weisinger ◽  
C. L. Milanes ◽  
V. Sylva ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Metabolic Acidosis ◽  
Adenylate Cyclase ◽  
Receptor Binding ◽  
Binding Capacity ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Serum Bicarbonate ◽  
Blood Ph

The phosphaturic action of parathyroid hormone (PTH) is blunted during metabolic acidosis. Previous studies suggest that the activation of renal cortical adenylate cyclase by PTH is decreased under this condition. However, the mechanisms underlying the defect are not completely defined. The present studies were designed to examine the interaction of PTH with its receptor-adenylate cyclase system in basolateral cortical membranes from dogs with metabolic acidosis. Chronic metabolic acidosis was induced in seven normal dogs. Venous blood pH decreased to 7.21 +/- 0.01 and serum bicarbonate to 12.58 +/- 0.32 meq/liter. In seven control dogs blood pH was 7.38 +/- 0.002 and serum bicarbonate was 20.14 +/- 0.26 meq/liter. The kidneys were surgically removed and basolateral membranes were prepared by differential centrifugation and ultracentrifugation in discontinuous sucrose density gradients for studies of adenylate cyclase activity and hormone-receptor binding. Metabolic acidosis resulted in a significant decrease in PTH-dependent adenylate cyclase activity (Vmax 2,119 +/- 150 pmol cAMP X mg prot-1 .30 min-1 vs. 3,548 +/- 116 in the controls). The PTH concentration giving half-maximal activation of adenylate cyclase was unchanged. However, PTH-receptor binding showed similar affinity and binding capacity in both groups of membranes. Basal enzyme activity was also similar. In the presence of the GTP analogue 5'-guanylylimidodiphosphate, PTH-dependent adenylate cyclase activity remained markedly decreased in the acidotic dog membranes compared with the controls. The ability of NaF to stimulate enzyme activity was also depressed in the membrane of acidotic dogs. Enzyme activity in the presence of Mn2+ was similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate cyclase activity in Y1 mouse adrenocortical tumor cells: some properties of the enzyme associated with purified plasma membrane fractions

1983 ◽  
Vol 61 (7) ◽  
pp. 547-552 ◽  
Author(s):  
Bernard P. Schimmer
Keyword(s):  
Plasma Membrane ◽  
Adenylate Cyclase ◽  
Plasma Membranes ◽  
Tumor Cell Line ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Adenylate Cyclase System ◽  
Adrenocortical Tumor ◽  
Intact Cells ◽  
Order Of Magnitude

Fractions enriched in plasma membranes were prepared from the Y1 mouse adrenocortical tumor cell line and were characterized with respect to adenylate cyclase activity. Optimal requirements of the adenylate cyclase system for guanyl nucleotides, Mg2+, ATP, and corticotropin (ACTH) were determined. The sensitivity of the adenylate cyclase system to ACTH1–24 in plasma membrane fractions was comparable with that observed in isolated intact cells. Polycations such as poly-L-arginine and histone competitively inhibited the action of ACTH1–24, supporting the view that the affinity of ACTH for the adenylate cyclase system is determined by the basic core of amino acids at residues 15–18. ACTH1–24 was at least one order of magnitude more potent than ACTH1–39 in stimulating adenylate cyclase activity in plasma membrane fractions.

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