Ca2+-induced inhibition of adenylyl cyclase in turkey erythrocyte membranes. 1998

E Demirel, and O Ugur, and H O Onaran
Department of Pharmacology and Clinical Pharmacology, Medical Faculty of Ankara University, Ankara, Turkey.

We investigated the effects of calcium ions (Ca2+) on the adenylyl cyclase activity in purified turkey erythrocyte membranes. Results showed the following: (i) Ca2+ inhibits cAMP accumulation stimulated by isoproterenol (1 micromol/l), NaF + AlCl3 (10 mmol/l + 20 micromol/l) or forskolin (10 micromol/l) in EGTA-washed turkey erythrocyte membranes. IC50 of free [Ca2+] is approximately 0.1 mmol/l in the presence of Mg2+ (2.5 mmol/l) and isobutylmethylxanthine (1 mmol/l). (ii) The potency of Ca2+ to inhibit cAMP accumulation is independent of the type of stimulus used to activate the adenylyl cyclase. We also evaluated the calcium sensitivity of the basal cAMP accumulation in the presence of GTP (10 micromol/l) and Mg2+ (2.5 mmol/l) which was also inhibited by Ca2+ with the same potency. (iii) The inhibition pattern of cAMP accumulation is not affected by the presence of added calmodulin (100 nmol/l). (iv) Ca2+ is ineffective on the binding of isoproterenol to the beta-adrenoceptors. (v) Increasing the concentration of Ca2+ does not induce an observable activation of cyclic nucleotide phosphodiesterase in the present experimental conditions. Thus, we concluded that the inhibition of cAMP accumulation is due to an inhibition of the adenylyl cyclase rather than the activation of phosphodiesterase(s). The presence of a yet unidentified isoform of adenylyl cyclase that can be directly inhibited by Ca2+ or a Gi protein that can be activated by Ca2+ seems to explain these results. In either case, these results provide an additional mode of cross-talk that can take place between the Ca2+- and cAMP-signaling systems.

UI MeSH Term Description Entries
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004910 Erythrocyte Membrane The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS. Erythrocyte Ghost,Red Cell Cytoskeleton,Red Cell Ghost,Erythrocyte Cytoskeleton,Cytoskeleton, Erythrocyte,Cytoskeleton, Red Cell,Erythrocyte Cytoskeletons,Erythrocyte Ghosts,Erythrocyte Membranes,Ghost, Erythrocyte,Ghost, Red Cell,Membrane, Erythrocyte,Red Cell Cytoskeletons,Red Cell Ghosts
D000067956 Adenylyl Cyclase Inhibitors Compounds that bind to and inhibit the action of ADENYLYL CYCLASES. Adenylate Cyclase Inhibitors,Cyclase Inhibitors, Adenylate,Cyclase Inhibitors, Adenylyl,Inhibitors, Adenylate Cyclase,Inhibitors, Adenylyl Cyclase
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000262 Adenylyl Cyclases Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP. Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014422 Turkeys Large woodland game BIRDS in the subfamily Meleagridinae, family Phasianidae, order GALLIFORMES. Formerly they were considered a distinct family, Melegrididae. Meleagridinae,Meleagrididae
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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