scholarly journals An investigation of the involvement of adenosine 3′:5′-cyclic monophosphate in steroidogenesis by using isolated adrenal cell column perfusion

1975 ◽  
Vol 148 (3) ◽  
pp. 539-544 ◽  
Author(s):  
A M Hudson ◽  
C McMartin
Keyword(s):  
Cyclic Amp ◽  
Inverse Relationship ◽  
Time Lag ◽  
Inhibitory Effect ◽  
Cell Column ◽  
Response Curves ◽  
Steroid Production ◽  
Adrenal Cell ◽  
Narrow Concentration Range ◽  
Range Variation

The involvement of cyclic AMP in corticosteroidogenesis was investigated by using isolated adrenal cell column perfusion. Steroids were produced in response to 0.5, 1.0 and 5.0 mg of cyclic AMP/ml. Analysis of the shape of the response curves indicated an inverse relationship between rate of onset of steroid production and dose. A further increase in steroid production during the washout period after the 5 mg/ml dose was considered to indicate an intracellular inhibitory effect of cyclic AMP. Release of cyclic AMP into the perfusate only occurred in response to supramaximal steroidogenic doses of ACTH (adrenocorticotrophin). A connexion between dose and response was demonstrated over a narrow concentration range. Variation in the time-lag before cyclic AMP production and in the duration of the response was marked; further, no reproducible ratio of steroid output to cyclic AMP output was shown at any level of stimulation. These results are discussed together with those of other recent investigations. It is considered that these findings do not support an obligatory role for cyclic AMP as mediator of ACTH action in the adrenal.

Conversion of 22S-hydroxy-cholesterol and its effect on the metabolism of other sterols in rat adrenal cells and bovine adrenal mitochondria

1982 ◽  
Vol 100 (4) ◽  
pp. 599-605 ◽  
Author(s):  
J. G. M. Huijmans ◽  
H. J. Degenhart ◽  
D. J. Kortleve
Keyword(s):  
Causal Relationship ◽  
Enzyme System ◽  
Inhibitory Effect ◽  
Side Chain ◽  
Steroid Production ◽  
Adrenal Cell ◽  
Adrenal Cells ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Isolated Rat

Abstract. This study provides evidence that 22S-OH-cholesterol inhibits the conversion of 25-OH-cholesterol but has no effect on the conversion of 22R-OH-cholesterol. The latter sterol is an intermediate in the cholesterol side-chain cleavage, whereas for the conversion of 25-OH-cholesterol into pregnenolone the complete side-chain cleaving enzyme system is necessary. This complements a previous study in which it was shown, that 22S-OH-cholesterol has an inhibitory effect on the ACTH-induced conversion of cholesterol into corticosterone in isolated rat adrenal cells. The available evidence thus suggests an inhibition by 22S-OH-cholesterol of the first step in the cholesterol side-chain cleavage. The results, obtained from the experiments with rat adrenal cells and with bovine adrenal mitochondria, allow the hypothesis, that a causal relationship exists between conversion of 22S-OH-cholesterol and production of corticosterone, respectively pregnenolone. We conclude, that 22S-OH-cholesterol is a substrate for steroid production in the adrenal cell. This sterol inhibits the ACTH-stimulated corticosterone production. The site of this inhibition is located at one of the first steps in the cholesterol side-chain cleavage, probably the binding of cholesterol to the cytochrome P450-complex.

scholarly journals Caffeine inhibits cytosolic calcium oscillations induced by noradrenaline and vasopressin in rat hepatocytes

1994 ◽  
Vol 301 (3) ◽  
pp. 737-744 ◽  
Author(s):  
L Combettes ◽  
B Berthon ◽  
M Claret
Keyword(s):  
Cyclic Amp ◽  
Single Cells ◽  
Rat Hepatocytes ◽  
Cytosolic Calcium ◽  
Inhibitory Effect ◽  
Calcium Oscillations ◽  
Direct Inhibition ◽  
Response Curves ◽  
Release Channel ◽  
Induced Changes

The effects of caffeine on agonist-induced changes in intracellular Ca2+ concentration ([Ca2+]i) were studied in single fura 2-loaded cells and suspensions of rat hepatocytes. In single cells, caffeine (5-10 mM) inhibited [Ca2+]i oscillations induced both by noradrenaline (0.1 microM) and by vasopressin (0.1 nM). Caffeine shifted the dose-response curves of the [Ca2+]i rise induced by vasopressin (0.5 to 2 nM) and noradrenaline (from 80 to 580 nM) in suspensions of liver cells loaded with quin2. This inhibitory effect of caffeine was not due to inhibition of phosphodiesterase enzymes and elevation of cyclic AMP levels, because application of 3-isobutyl-1-methylxanthine, forskolin or 8-bromo cyclic AMP had no inhibitory effect on the intracellular Ca2+ rise induced by inositol 1,4,5-trisphosphate (InsP3)-dependent agonists. We demonstrate that the inhibitory effect of caffeine may result from at least three actions of caffeine: (1) inhibition of receptor-stimulated InsP3 formation; (2) inhibition of agonist-stimulated Ca2+ influx; and (3) direct inhibition of the InsP3-sensitive Ca(2+)-release channel.

Antagonistic control of fluid secretion by the Malpighian tubules ofTenebrio molitor: effects of diuretic and antidiuretic peptides and their second messengers

2002 ◽  
Vol 205 (4) ◽  
pp. 493-501 ◽  
Author(s):  
U. I. M. Wiehart ◽  
S. W. Nicolson ◽  
R. A. Eigenheer ◽  
D. A. Schooley
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Second Messengers ◽  
Fluid Secretion ◽  
Tenebrio Molitor ◽  
Inhibitory Effect ◽  
Malpighian Tubules ◽  
Dependent Manner ◽  
Response Curves

SUMMARYFluid secretion by insect Malpighian tubules is controlled by haemolymph-borne factors. The mealworm Tenebrio molitor provides the first known example of antagonistic interactions between endogenous neuropeptides acting on Malpighian tubules. The two corticotropin-releasing-factor (CRF)-related diuretic peptides previously isolated from Tenebrio molitor, Tenmo-DH37 and Tenmo-DH47, were found to stimulate Tenebrio molitor tubules in vitro in a dose-dependent manner with EC50 values of 0.12 nmol l–1 and 26 nmol l–1 respectively. However, no synergistic or additive effect was observed when these two peptides were tested simultaneously. We then investigated antagonism between second messengers: dose–response curves were constructed for stimulation of Tenebrio molitor tubules by cyclic AMP and their inhibition by cyclic GMP. When both cyclic nucleotides were included in the bathing Ringer, the stimulatory effect of cyclic AMP was neutralised by cyclic GMP. Similarly, the stimulatory effect of Tenmo-DH37 was reversed on addition of an antidiuretic peptide (Tenmo-ADF), which was recently isolated from Tenebrio molitor and acts via cyclic GMP. The cardioacceleratory peptide CAP2b, originally isolated from Manduca sexta, also increases intracellular cyclic GMP levels and inhibited fluid secretion by Tenebrio molitor tubules, with an EC50 value of 85 nmol l–1. This inhibitory effect was reversed by Tenmo-DH37. Endogenous diuretic and antidiuretic peptides, effective at low concentrations and acting via antagonistic second messengers, have the potential for fine control of secretion rates in the Malpighian tubules of Tenebrio molitor.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

Effect of Cyclic AMP and Cyclic GMP on Thromboplastin (Factor III) Synthesis in Human Monocytes In Vitro

1983 ◽  
Vol 50 (04) ◽  
pp. 804-809 ◽  
Author(s):  
Torstein Lyberg
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Immune Complexes ◽  
Phosphodiesterase Inhibitors ◽  
Inhibitory Effect ◽  
Intracellular Camp ◽  
Human Monocytes ◽  
Purified Protein Derivative ◽  
A 23187

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.

scholarly journals Receptor-mediated gonadotropin action in the ovary. Inhibitory actions of concanavalin A and wheat-germ agglutinin on gonadotropin-stimulated cyclic AMP and progesterone responses in ovarian cells

1981 ◽  
Vol 200 (1) ◽  
pp. 153-159 ◽  
Author(s):  
S Azhar ◽  
K M Menon
Keyword(s):  
Cyclic Amp ◽  
Concanavalin A ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Carbohydrate Chain ◽  
Inhibitory Effect ◽  
Dolichos Biflorus ◽  
Acetylneuraminic Acid ◽  
Ovarian Cells ◽  
Proline Incorporation

Pretreatment of ovarian cells with concanavalin A and wheat-germ agglutinin blocked the gonadotropin-induced cyclic AMP and progesterone responses and this effect was time- and concentration-dependent. Basal production of either cyclic AMP or progesterone, however, was not affected by treatment of cells with lectin. The effect of concanavalin A on gonadotropin-mediated cyclic AMP and progesterone responses was blocked by alpha-methyl D-mannoside and alpha-methyl d-glucoside. Similarly the inhibitory effect of wheat-germ agglutinin was reversed by N-acetyl-D-glucosamine. Pretreatment of ovarian cells with concanavalin A or wheat-germ agglutinin had no effect on protein synthesis in the ovary as monitored by [3H]proline incorporation studies. Concanavalin A and wheat-germ agglutinin did not affect steroid production in response to dibutyryl cyclic AMP and 8-bromo cyclic AMP, indicating that the inhibitory action of lectin was occurring at a step before cyclic AMP formation. Lectins specific for L-fucose, D-galactose and N-acetyl-D-galactosamine, gorse seed agglutinin, peanut agglutinin and Dolichos biflorus agglutinin respectively, did not interfere with gonadotropin-induced cyclic AMP and progesterone responses. The present studies suggest that gonadotropin receptors may be glycoprotein in nature or closely associated with glycoprotein structures with the carbohydrate chain containing N-acetyl-D-glucosamine, mannose and possibly N-acetylneuraminic acid.

Pharmacological characterization of cyclic AMP receptors mediating gene regulation in Dictyostelium discoideum

1986 ◽  
Vol 6 (7) ◽  
pp. 2402-2408
Author(s):  
B Haribabu ◽  
R P Dottin
Keyword(s):  
Gene Expression ◽  
Cyclic Amp ◽  
Cell Surface ◽  
Dictyostelium Discoideum ◽  
Cell Surface Receptor ◽  
Intracellular Camp ◽  
Response Curves ◽  
Pharmacological Characterization ◽  
Surface Receptor ◽  
Extracellular Molecules

Extracellular molecules regulate gene expression in eucaryotes. Exogenous cyclic AMP (cAMP) affects the expression of a large number of developmentally regulated genes in Dictyostelium discoideum. Here, we determine the specificity of the receptor(s) which mediates gene expression by using analogs of cAMP. The order of potency with which these analogs affect the expression of specific genes is consistent with the specificity of their binding to a cell surface receptor and is distinct from their affinity for intracellular cAMP-dependent protein kinase. Dose-response curves with cAMP and adenosine 3',5'-monophosphorothioate, a nonhydrolyzable analog, revealed that the requirement for high concentrations of exogenous cAMP for regulating gene expression is due to the rapid degradation of cAMP by phosphodiesterase. The addition of low concentrations of cAMP (100 nM) or analogs in pulses also regulates gene expression. Both the genes that are positively regulated by exogenous cAMP and the discoidin gene, which is negatively regulated, respond to cAMP analogs to the same degree. Genes expressed in prespore or prestalk cells are also similarly regulated. These data suggest that the effects are mediated through the same receptor. The specificity of this receptor is indistinguishable from that of the well-characterized cell surface cAMP receptor.

Effect of sodium fluoride on concentrating and diluting ability in the rat

1977 ◽  
Vol 232 (4) ◽  
pp. F335-F340 ◽  
Author(s):  
J. D. Wallin ◽  
R. A. Kaplan
Keyword(s):  
Cyclic Amp ◽  
Urine Volume ◽  
Free Water ◽  
Urine Osmolality ◽  
Inhibitory Effect ◽  
Sprague Dawley ◽  
Free Water Clearance ◽  
Sprague Dawley Rats ◽  
Direct Inhibitory Effect ◽  
Hereditary Hypothalamic Diabetes Insipidus

Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.

Control of brown adipose tissue lipolysis and respiration by adenosine

1983 ◽  
Vol 245 (6) ◽  
pp. E555-E559 ◽  
Author(s):  
D. Szillat ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Palmitic Acid ◽  
Brown Adipose Tissue ◽  
Brown Adipocyte ◽  
Tissue Respiration ◽  
Dibutyryl Cyclic Amp ◽  
Response Curves ◽  
Brown Adipose ◽  
Stimulation Of

Adenosine competitively inhibited the stimulatory effects of (-)-isoproterenol on lipolysis and respiration in hamster brown adipocytes. The low value of the apparent ki for respiratory inhibition by adenosine (7 nM) indicated that the nucleoside may control brown adipocyte function under physiological concentrations. Significantly, the dose-response curves for isoproterenol stimulation of lipolysis and respiration were both shifted by adenosine to higher agonist concentrations by the same order of magnitude, providing additional evidence for a tight coupling between lipolysis and respiration. The inhibitory effects of adenosine were rapidly reversed by a) adenosine deaminase, b) agents known to increase intracellular cyclic AMP levels (isoproterenol, isobutylmethylxanthine, dibutyryl cyclic AMP), and c) direct stimulation of respiration with palmitic acid. These results, combined with the fact that adenosine failed to affect respiration evoked either by dibutyryl cyclic AMP or by palmitic acid, strongly indicate that adenosine regulates brown adipose tissue respiration at an early metabolic step of the stimulus-thermogenesis sequence, most probably at the level of the adenylate cyclase complex.

scholarly journals Oscillations of cyclic nucleotide concentrations in relation to the excitability of Dictyostelium cells

1979 ◽  
Vol 81 (1) ◽  
pp. 33-47 ◽  
Author(s):  
G. Gerisch ◽  
D. Malchow ◽  
W. Roos ◽  
U. Wick
Keyword(s):  
Signal Processing ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Inhibitory Effect ◽  
Camp Concentration ◽  
Surface Receptors ◽  
Camp Generation ◽  
Adenylate Cyclase Activation ◽  
Signal Input ◽  
Extracellular Camp

Aggregating cells of Dictyostelium discoideum are able to release cyclic AMP periodically. The oscillations of cAMP generation are associated with changes in adenylate cyclase activity. Cyclic AMP receptors on the cell surface are functionally coupled to the oscillating system as evidenced by phase shifts that are induced by small pulses of extracellular cAMP. An important element of the oscillating system is the signal processing from surface receptors to the adenylate cyclase. This pathway exhibits adaptation resulting in the suppression of responses to constant, elevated concentrations of cAMP. The signal input for adenylate cyclase activation is, therefore, a change in the extracellular cAMP concentration with time. Oscillations in the absence of detectable changes of intra- or extracellular cAMP concentrations suggest the possibility that there is a metabolic network in D. discoideum cells that undergoes oscillations without coupling to adenylate cyclase. Cyclic GMP concentrations oscillate with a slight phase difference in advance of that of cAMP, suggesting that the two nucleotide cyclases might not be activated by the same mechanism. Elevation of extracellular calcium exerts an inhibitory effect on the accumulation of cAMP and on the second of the two cGMP peaks.

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