scholarly journals Regulation of ciliary adenylate cyclase by Ca2+ in Paramecium

1987 ◽  
Vol 246 (2) ◽  
pp. 337-345 ◽  
Author(s):  
M C Gustin ◽  
D L Nelson
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Guanylate Cyclase ◽  
Cyclic Nucleotides ◽  
Second Messengers ◽  
Active Agent ◽  
Ciliated Protozoan ◽  
Calmodulin Antagonists ◽  
Ciliary Membrane ◽  
Ca2 Channels

In the ciliated protozoan Paramecium, Ca2+ and cyclic nucleotides are believed to act as second messengers in the regulation of the ciliary beat. Ciliary adenylate cyclase was activated 20-30-fold (half-maximal at 0.8 microM) and inhibited by higher concentrations (10-20 microM) of free Ca2+ ion. Ca2+ activation was the result of an increase in Vmax., not a change in Km for ATP. The activation by Ca2+ was seen only with Mg2+ATP as substrate; with Mn2+ATP the basal adenylate cyclase activity was 10-20-fold above that with Mg2+ATP, and there was no further activation by Ca2+. The stimulation by Ca2+ of the enzyme in cilia and ciliary membranes was blocked by the calmodulin antagonists calmidazolium (half-inhibition at 5 microM), trifluoperazine (70 microM) and W-7 (50-100 microM). When ciliary membranes (which contained most of the ciliary adenylate cyclase) were prepared in the presence of Ca2+, their adenylate cyclase was insensitive to Ca2+ in the assay. However, the inclusion of EGTA in buffers used for fractionation of cilia resulted in full retention of Ca2+-sensitivity by the ciliary membrane adenylate cyclase. The membrane-active agent saponin specifically suppressed the Ca2+-dependent adenylate cyclase without inhibiting basal activity with Mg2+ATP or Mn2+ATP. The ciliary adenylate cyclase was shown to be distinct from the Ca2+-dependent guanylate cyclase; the two activities had different kinetic parameters and different responses to added calmodulin and calmodulin antagonists. Our results suggest that Ca2+ influx through the voltage-sensitive Ca2+ channels in the ciliary membrane may influence intraciliary cyclic AMP concentrations by regulating adenylate cyclase.

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.

scholarly journals Special Issue on “New Advances in Cyclic AMP Signalling”—An Editorial Overview

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2274
Author(s):  
Stephen John Yarwood
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclic Nucleotides ◽  
Adenosine Monophosphate ◽  
Mechanisms Of Action ◽  
Effector Proteins ◽  
Cell Type ◽  
Special Issue ◽  
New Techniques ◽  
Cell Type Specific

The cyclic nucleotides 3′,5′-adenosine monophosphate (cyclic AMP) signalling system underlies the control of many biological events and disease processes in man. Cyclic AMP is synthesised by adenylate cyclase (AC) enzymes in order to activate effector proteins and it is then degraded by phosphodiesterase (PDE) enzymes. Research in recent years has identified a range of cell-type-specific cyclic AMP effector proteins, including protein kinase A (PKA), exchange factor directly activated by cyclic AMP (EPAC), cyclic AMP responsive ion channels (CICs), and the Popeye domain containing (POPDC) proteins, which participate in different signalling mechanisms. In addition, recent advances have revealed new mechanisms of action for cyclic AMP signalling, including new effectors and new levels of compartmentalization into nanodomains, involving AKAP proteins and targeted adenylate cyclase and phosphodiesterase enzymes. This Special Issue contains 21 papers that highlight advances in our current understanding of the biology of compartmentlised cyclic AMP signalling. This ranges from issues of pathogenesis and associated molecular pathways, functional assessment of novel nanodomains, to the development of novel tool molecules and new techniques for imaging cyclic AMP compartmentilisation. This editorial aims to summarise these papers within the wider context of cyclic AMP signalling.

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 The metabolism of cyclic nucleotides in the guinea-pig pancreas. Adenylate cyclase and guanylate cyclase

1980 ◽  
Vol 186 (2) ◽  
pp. 499-505 ◽  
Author(s):  
M Lemon ◽  
P Methven ◽  
K Bhoola
Keyword(s):  
Adenylate Cyclase ◽  
Guinea Pig ◽  
Guanylate Cyclase ◽  
Cyclic Nucleotides ◽  
Cyclase Activity ◽  
Dependent Manner ◽  
Guanylate Cyclase Activity ◽  
Triton X ◽  
Dose Dependent ◽  
Significant Activation

Adenylate cyclase from the guinea-pig pancreas was activated in a dose-dependent manner by both secretin and cholecystokinin-pancreozymin, but in contrast with results in other species the hormones were approximately equipotent. All other hormones and transmitter substances tested were without any effect on adenylate cyclase activity. Guanylate cyclase activity was shown to have both particulate and supernatant components in the guinea-pig pancreas. The particulate enzyme, but not the supernatant enzyme, was markedly activated by Triton X-100, and most of the induced activity was released into the supernatant. The supernatant enzyme was specifically Mn2+-dependent, but, even though Mn2+ was maximally effective at a concentration of 3 mM, activity could be raised further by increasing Ca2+ concentration. The particulate enzyme, by contrast, was relatively Mn2+-independent. Activity of the particulate guanylate cyclase was enhanced by phosphatidylserine. The supernatant enzyme displayed classical Michaelis-Menten kinetics, but the particulate enzyme deviated markedly from such kinetics. Under none of the conditions used was any significant activation of guanylate cyclase observed with any of the secretogen hormones or transmitter substances.

Cytochemical Localization of Guanylate and Adenylate Cyclase in Photoreceptor Cells of the Fly

1995 ◽  
Vol 50 (9-10) ◽  
pp. 695-698 ◽  
Author(s):  
Ulrich Schraermeyer ◽  
Hennig Stieve ◽  
Michael Rack
Keyword(s):  
Spatial Distribution ◽  
Adenylate Cyclase ◽  
Guanylate Cyclase ◽  
Cyclic Nucleotides ◽  
Photoreceptor Cells ◽  
Cytochemical Localization ◽  
Calliphora Erythrocephala ◽  
Cytochemical Method ◽  
Enzyme Cascade

Abstract In photoreceptor cells of invertebrates light triggers an enzyme cascade in which the phos-phoinositide pathway is crucially involved. Likewise, there is growing evidence of an impor­ tant role of cyclic nucleotides, too. To localize these enzymes able to catalyze the formation of cGM P and cAMP, the spatial distribution of guanylate cyclase (EC 4.6.1.2) and adenylate cyclase (EC 4.6.1.1) was determined in photoreceptor cells of the fly. In photoreceptor cells of the blowfly (Calliphora erythrocephala), the electron dense reaction product of guanylate cyclase was found within the phototransducing region, the rhabdomeral microvilli and in the mitochondria. Staining was also observed throughout the cytoplasm of the microvilli. With the same cytochemical method, reaction product for adenylate cyclase was found on the tips of the photosensory membrane, and not in the cytoplasm of the rhabdomeral microvilli. The results presented here further argue for an important role of one or possibly two cyclic nucleotides in the photoreceptor cells, and possibly in the process of phototransduction of in­ vertebrates.

scholarly journals Cyclic Nucleotides in Platelet Function

1977 ◽  
Author(s):  
R.J. Haslam
Keyword(s):  
Platelet Aggregation ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Recent Work ◽  
Mechanism Of Action ◽  
Cyclic Gmp ◽  
Cyclic Nucleotides ◽  
Platelet Membrane ◽  
Phosphodiesterase 3 ◽  
Lines Of Evidence

Five lines of evidence indicate that cyclic AMP mediates the effects on platelets of inhibitory agonists, such as PGE1 and adenosine. Thus, these compounds activate adenylate cyclase in platelet particulate fractions (1) and increase cyclic AMP levels in intact platelets (2), while their effects are potentiated by inhibitors of cyclic AMP phosphodiesterase (3), are blocked by inhibitors of adenylate cyclase (4) and are mimicked by analogues of cyclic AMP (5). Apparent discrepancies between platelet cyclic AMP levels and the inhibition of aggregation can be explained by the ability of some aggregating agents to prevent increases in cyclic AMP and by postulating a delay before the effect of a change in platelet cyclic AMP level is expressed. A mechanism of action for cyclic AMP is suggested by observations that it causes phosphorylation of platelet membrane proteins and increases the uptake of Ca2+ ions by platelet membrane fractions. Studies on the effects of aggregating agents on cyclic AMP levels in resting platelets have given variable results but recent work indicating that compounds that can inhibit adenylate cyclase in intact platelets neither cause nor reproducibly potentiate aggregation or release suggests that cyclic AMP plays no role in the responses of platelets to aggregating agents, unless the platelet cyclic AMP level is elevated above resting values. Studies on platelet cyclic GMP levels have shown that increases usually occur in association with both platelet aggregation and the release reaction. While these findings are consistent with some role for cyclic GMP in these processes, conditions have been found in which some aggregation and release can occur without increases in cyclic GMP. In general, the available evidence suggests that Ca2+ ions are likely to be more important than cyclic GMP in mediating platelet responses.

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