Simple fluctuation of Ca2+ elicits the complex circadian dynamics of cyclic AMP and cyclic GMP in Paramecium

1999 ◽  
Vol 112 (2) ◽  
pp. 201-207 ◽  
Author(s):  
K. Hasegawa ◽  
H. Kikuchi ◽  
S. Ishizaki ◽  
A. Tamura ◽  
Y. Tsukahara ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Concentration Camp ◽  
Dark Cycle ◽  
Camp Concentration ◽  
Mathematical Functions ◽  
Camp And Cgmp ◽  
Different Levels

The circadian dynamics of cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP) were simulated in Paramecium multimicronucleatum. The mathematical functions determined closely mimic the Ca2+ dependence of adenylate cyclase (AC) and guanylate cyclase (GC) activities as documented in P. tetraurelia. Patterns of cAMP concentration ([cAMP]), cGMP concentration ([cGMP]), and the ratio [cGMP]/[cAMP] were calculated with respect to Ca2+ concentrations ([Ca2+]) fluctuating sinusoidally with a period of 24 hours at three different levels: low, medium, and high. The functions displayed varying patterns of [cAMP] characteristic for [Ca2+] fluctuating at each level, while patterns of [cGMP] and [cGMP]/[cAMP] almost paralleled [Ca2+] fluctuations. Similar patterns were observed for actual [cAMP] and [cGMP] measured during the light/dark cycle in P. multimicronucleatum, grown in axenic media additionally containing [Ca2+] at 25 (low), 100 (medium), or 400 (high) microM, respectively. The coincidence between simulated and measured fluctuations of [cAMP] and [cGMP] suggests that the circadian fluctuations of intracellular [Ca2+] primarily stimulate activities of AC and GC via their different degrees of Ca2+ dependence, which are ultimately responsible for the circadian spatiotemporal organization of various physiological functions in Paramecium.

REGULATION OF RECEPTOR-OPERATED Ca2− CHANNEL OPENING IN HUMAN PLATELETS

1987 ◽  
Author(s):  
Katrina J Moffat ◽  
D Euan MacIntyre
Keyword(s):  
Adenylate Cyclase ◽  
Contrast Agents ◽  
Guanylate Cyclase ◽  
Receptor Occupancy ◽  
Human Platelets ◽  
Regulatory Mechanisms ◽  
Receptor Interaction ◽  
Thrombin Receptors ◽  
Channel Opening ◽  
Camp And Cgmp

Agonist-induced elevation of the platelet intracellular free Ca2+ concentration ([Ca2−]i), as monitored using quin2, is not electrically mediated and is attenuated by removal of extracellular Ca2− and by lanthanides (e.g Gd3−).Collectively these data suggest that elevation of [Ca2−]i in platelets derives in part via influx of external Ca2−presumably through a receptor-operated Ca2− channel (ROC). Hal lam & Rink (FEBS Lett. 186: 175: 1985) showed that Mn2−also enters platelets via these ROC. To investigate the possible regulatory mechanisms that govern ROC status, we utilized quin2-labelled human platelets suspended in a Ca2+-free Hepes buffered Tyrodes solution, and monitored agonist-induced Mn2+-mediated quenching of quin2 fluorescence as an index of ROC opening.Thrombin (Th, 0.01-1 U/ml), Vasopressin (VP, 10-1000 nM) and the TxA2-mitnetic, EP171 (1-100 nM) all induced ROC opening which occurred rapidly (<30s), was maximal within 30-60s and thereafter declined. Gd3+ (≤2 mM) markedly impaired this Mn2ࢤ-mediated quenching of quin2 fluorescence induced by all 3 agonists. The adenylate cyclase stimulant PGD2 (3-3000 nM) and the guanylate cyclase stimulant sodium nitroprusside (0.01-10 μM) impaired ROC opening induced by Th (0.5 U/ml), VP (100 nM) and EP171 (25 nM) whether added to platelets ≤120sbefore or 30s after the agonists. In contrast, agents that selectively antagonize, at the receptor level, the effects of VP (e.g. d(CH2)5Tyr Me AVP, 10 ¼H) or EP171 (e.g.EP092, 250nM), or that inhibit the action of Th(e.g. Hirudin 1 U/ml)only impaired ROC opening when added to platelets simultaneously with or before the agonist.These results indicate that, although initiated by agonist-receptor interaction, maintenance of the open state of ROC in human platelets does not require continued receptor occupancy or activation by agonist. Moreover, besides acting to impair the transduction processes initiated following occupancy by agonist of platelet Vi, TP and Thrombin receptors, cAMP-and cGMP-dependent reactions also can terminate or otherwise limit opening of ROC.

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.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

1979 ◽  
Vol 237 (5) ◽  
pp. C200-C204 ◽  
Author(s):  
D. J. Stewart ◽  
J. Sax ◽  
R. Funk ◽  
A. K. Sen
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Salt Gland ◽  
Domestic Ducks ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

scholarly journals THE MODULATING INFLUENCE OF CYCLIC NUCLEOTIDES UPON LYMPHOCYTE-MEDIATED CYTOTOXICITY

1973 ◽  
Vol 138 (2) ◽  
pp. 381-393 ◽  
Author(s):  
Terry B. Strom ◽  
Charles B. Carpenter ◽  
Marvin R. Garovoy ◽  
K. Frank Austen ◽  
John P. Merrill ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclic Gmp ◽  
Cyclic Nucleotides ◽  
Prostaglandin E1 ◽  
Cell Interaction ◽  
Target Cells ◽  
Cholinergic Stimulation ◽  
Initial Cell ◽  
Initial Interaction

The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor alloantigens is modulated by the cellular levels of cyclic AMP and cyclic GMP. Increases in the cyclic AMP levels of attacking lymphocytes by stimulation with prostaglandin E1, isoproterenol, and cholera toxin inhibit lymphocyte-mediated cytotoxicity; whereas, depletion of cyclic AMP with imidazole enhances cytotoxicity. The augmentation of cytotoxicity produced by cholinergic stimulation with carbamylcholine is not associated with alterations in cyclic AMP levels and is duplicated by 8-bromo-cyclic GMP. The effects of activators of adenylate cyclase, cholinomimetic agents, and 8-bromocyclic GMP are upon the attacking and not the target cells and occur at the time of initial interaction of attacking and target cells. Indeed, the level of cyclic nucleotide (cyclic AMP and cyclic GMP) at the time of initial cell-to-cell interaction determines the extent of cytotoxicity.

scholarly journals Adenylate cyclase, guanylate cyclase and cyclic nucleotide phosphodiesterases of guinea-pig cardiac sarcolemma

1976 ◽  
Vol 158 (3) ◽  
pp. 535-541 ◽  
Author(s):  
P J St Louis ◽  
P V Sulakhe
Keyword(s):  
Adenylate Cyclase ◽  
Guinea Pig ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Maximal Activity ◽  
Cardiac Sarcolemma ◽  
Guinea Pig Heart ◽  
Membrane Bound ◽  
Triton X ◽  
Assay Conditions

1. The activities of the enzymes involved in the metabolism of cyclic nucleotides were studied in sarcolemma prepared front guinea-pig heart ventricle; the enzyme activities reported here were linear under the assay conditions. 2. Adenylate cyclase was maximally activated by 3mM-NaF; NaF increased the Km for ATP (from 0.042 to 0.19 mM) but decreased the Ka for Mg2+ (from 2.33 to 0.9 mM). In the presence of saturating Mg2+ (15 mM), Mn2+ enhanced adenylate cyclase, whereas Co2+ was inhibitory. beta-Adrenergic amines (10-50 muM) stimulated adenylate cyclase (38+/-2%). When added to the assay mixture, guanyl nucleotides (GTP and its analogue, guanylyl imidophosphate) stimulated basal enzyme activity and enhanced the stimulation by isoproterenol. By contrast, preincubation of sarcolemma with guanylyl imidodiphosphate stimulated the formation of an ‘activated’ form of the enzyme, which did not reveal increased hormonal sensitivity. 3. The guanylate cyclase present in the membranes as well as in the Triton X-100-solubilized extract of membranes exhibited a Ka for Mn 2+ of 0.3 mM; Mn2+ in excess of GTP was required for maximal activity. Solubilized guanylate cyclase was activated by Mg2+ only in the presence of low Mn2+ concentrations; Ca2+ was inhibitory both in the absence and presence of low Mn2+. Acetylcholine as well as carbamolycholine stimulated membrane-bound guanylate cyclase. 4. Cylic nucleotide phosphodiesterase activities of sarcolemma exhibited both high-and low-Km forms with cyclic AMP and with cyclic GMP as substrate. Ca2+ ions increased the Vmax. of the cyclic GMP-dependent enzyme.

scholarly journals Evidence for the involvement of cyclic AMP in the pheromonal modulation of barnacle settlement

1995 ◽  
Vol 198 (3) ◽  
pp. 655-664 ◽  
Author(s):  
A Clare ◽  
R Thomas ◽  
D Rittschof
Keyword(s):  
Signal Transduction ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclic Gmp ◽  
Phosphodiesterase Inhibitor ◽  
Balanus Amphitrite ◽  
Dibutyryl Cyclic Amp ◽  
Physico Chemical ◽  
Miconazole Nitrate

The involvement of cyclic AMP in the settlement of the cypris larva of Balanus amphitrite amphitrite Darwin has been examined through the use of compounds that affect intracellular cyclic AMP levels. The activation of adenylate cyclase with forskolin, and the inhibition of phosphodiesterase with 3-isobutyl-1-methylxanthine, caffeine and theophylline, significantly increased the settlement of cyprids. Although the analogue dibutyryl cyclic AMP appeared to increase settlement, the effect was not significant. No marked increase in settlement resulted from the incubation of cyprids with dibutyryl cyclic GMP, 8-(4-chlorophenylthio) (CPT) cyclic AMP or papaverine (a phosphodiesterase inhibitor). Miconazole nitrate, an adenylate cyclase inhibitor, prevented settlement, but this effect appeared to be physico-chemical rather than pharmacological. Radioimmunoassay did not clearly show whether cyclic AMP levels changed following exposure of cyprids to a pulse of crude barnacle extract. However, exposure to forskolin significantly increased the cyclic AMP titre of cyprids. We conclude that compounds that alter intracellular cyclic AMP levels alter normal patterns of cyprid settlement. Whether this is because of an alteration in signal transduction is unclear.

Positive inotropy due to lowering cyclic GMP is also mediated by increases in cyclic AMP in control and hypertrophic hearts

1998 ◽  
Vol 76 (6) ◽  
pp. 605-612 ◽  
Author(s):  
Karen L Naim ◽  
Prem Rabindranauth ◽  
Harvey R Weiss ◽  
James Tse ◽  
Richard J Leone, Jr. ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Current Model ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Control Group ◽  
Inotropic Effects ◽  
Significant Change

The aim of the current study was to determine if lowering myocardial cyclic GMP by guanylate cyclase inhibition would add independently to the positive inotropic effects caused by raising cyclic AMP and if these effects are modified in left ventricular hypertrophy (LVH) produced by aortic valve plication. Isoproterenol (ISO) (0.1 mg·kg-1·min-1) was infused into a branch of the left anterior descending coronary artery of seven control and eight hypertrophy open-chest anesthetized dogs. After 10 min, simultaneous infusion of methylene blue (MB) (2 mg·kg-1·min-1) was initiated at the same site. Hypertrophy increased heart weight and heart weight / body weight ratio. While both drugs increased left ventricular dP/dtmax, no additional global effects were observed in either group. Changes in regional variables followed the same pattern in both groups, i.e., ISO produced an increase that was enhanced by the addition of MB. ISO increased segment shortening, with a significant change in the control group. ISO increased regional force in both groups. The addition of MB increased force above ISO levels, with a significant change in the LVH group. ISO increased regional minute work (g·mm·min-1) (control, 1779 ± 428 to 2541 ± 500; LVH, 1157 ± 253 to 1839 ± 404) and O2 consumption. MB further increased regional work (control, 2993 ± 952; LVH, 2416 ± 853) and O2 consumption. ISO raised cyclic AMP (pmoles·g-1) (control, 468 ± 41 to 580 ± 84; LVH, 445 ± 43 to 562 ± 71) and had no effect on cyclic GMP (pmoles·g-1) (control, baseline 3.27 ± 0.22, ISO 2.87 ± 0.23; LVH, baseline 6.84 ± 1.12, ISO 5.66 ± 0.54). The addition of MB lowered cyclic GMP (control, 2.41 ± 0.26; LVH, 3.68 ± 0.35), but also increased cyclic AMP (control, 1021 ± 121; LVH, 1107 ± 134). Similar results were observed in control hearts using a specific soluble guanylate cyclase inhibitor (ODQ) in terms of changes in local work, O2 consumption, and cyclic nucleotides. Thus, at least part of the positive inotropic response to lowering cyclic GMP was mediated by changes in cyclic AMP in the current model. This was true in both control and LVH animals, although baseline cyclic GMP levels were higher, and a larger reduction in cyclic GMP was observed with MB in the LVH group.Key words: guanylate cyclase, coronary blood flow, myocardial shortening, myocardial work, myocardial O2 consumption, dog.

Hyperkalemia, hyperglycemia, and plasma levels of cyclic AMP and cyclic GMP induced by portal vein injection of cyclic nucleotides and their butyryl derivatives into dogs

1982 ◽  
Vol 60 (12) ◽  
pp. 1584-1591
Author(s):  
Toshikatsu Nakashima ◽  
Naofumi Morita ◽  
Yasumasa Nakanishi ◽  
Masayuki Inoki ◽  
Yutaka Kurogochi
Keyword(s):  
Blood Glucose ◽  
Plasma Level ◽  
Cyclic Amp ◽  
Portal Vein ◽  
Cyclic Gmp ◽  
Serum Potassium ◽  
Cyclic Nucleotides ◽  
Plasma Levels ◽  
Camp And Cgmp ◽  
Plasma Adenosine

The levels of serum potassium, blood glucose, and plasma adenosine cyclic 3′:5′-monophosphate (cAMP) and guanosine cyclic 3′:5′-monophosphate (cGMP) were studied after the portal vein injection of cyclic nucleotides and their derivatives, (cAMP, cGMP, N6, O2′,-dibutyryl adenosine 3′:5′-monophosphate (DBcAMP), N6-monobutyryl adenosine cyclic 3′:5′-monophosphate (NMBcAMP), and O2′-monobutyryl adenosine cyclic 3′:5′-monophosphate (OMBcAMP)), into dogs. Dose-related hyperglycemic responses were observed after the injection of DBcAMP (1–8 mg/kg). Transient and prominent hyperkalemia and hyperglycemia were caused by the injection of DBcAMP, NMBcAMP, and OMBcAMP (4 mg/kg). The hyperkalemic response was highest with NMBcAMP (1.22 mequiv./L), followed by OMBcAMP (0.64), DBcAMP (0.54), cGMP (0.47), and cAMP (0.41), whereas the hyperglycemic response was highest with NMBcAMP (146 mg/100 mL), followed by DBcAMP (93.6), OMBcAMP (77.1), and cAMP (56.0), and there was only a slight change with cGMP (28.4) compared with the control. The plasma level of cAMP was maximal with DBcAMP (1.92 nmol/mL), followed by NMBcAMP (1.28) and OMBcAMP (0.76), whereas the plasma levels of cGMP showed no evident change, except that caused by DBcAMP (0.27). Of the cyclic nucleotides tested, NMBcAMP was found to be most potent in causing both hyperkalemia and hyperglycemia. Based on these results, possible correlations between hyperkalemia, hyperglycemia, and plasma levels of cAMP and cGMP are discussed.

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