Biomaterial Database

Adrenalectomy-induced alterations of calmodulin-dependent hippocampal adenylate cyclase activity: role of guanine nucleotide-binding proteins. 1994

M N Gannon, and T Akompong, and M L Billingsley, and B S McEwen

Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10028.

Ca2+/calmodulin-dependent processes are altered by manipulations of the hypothalamic-pituitary-adrenal axis. In particular, adrenalectomy (ADX) attenuates hippocampal, but not cortical, calmodulin-dependent adenylate cyclase activity measured during the active (waking) phase of rats. The involvement of calmodulin- and guanine nucleotide (G)-binding proteins in the effects of ADX on the activity of calmodulin-dependent adenylate cyclase were investigated. In hippocampal membranes, inclusion of the GTP antagonist guanosine 5'-O-(2-thiodiphosphate) (250 microM) caused pronounced inhibition of calmodulin-stimulated adenylate cyclase activity. Guanosine 5(1)-O-(2-thiodiphosphate) had much smaller effects on calmodulin-independent (basal and forskolin-stimulated) enzyme activity. Substitution of Mn2+ for Mg2+ in the assay medium increased basal and forskolin-stimulated adenylate cyclase activity, but abolished calmodulin-dependent activation of this enzyme in both hippocampal and cortical membranes. These treatments blunted ADX-induced attenuation of hippocampal adenylate cyclase. ADX, with or without corticosterone administration (40 mg/kg, sc, once daily), failed to alter either Gi alpha or Gs alpha membrane protein content in either hippocampus or cortex. The levels of major membrane calmodulin-binding proteins in hippocampus and cortex also were not significantly altered by ADX. These results confirm that hormonal and biochemical regulation of calmodulin-dependent adenylate cyclase is distinct from that of other adenylate cyclase family members. Changes in Gs alpha and Gi alpha protein content alone cannot account for the effects of ADX on this enzyme. Overall, our studies suggest that the effects of ADX on calmodulin-dependent adenylate cyclase may occur through a reduction in the absolute amount of the catalytic subunit or an alteration(s) in the efficiency of coupling between adenylate cyclase and its modulators.

UI	MeSH Term	Description	Entries
D008274	Magnesium	A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008297	Male		Males
D008345	Manganese	A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
D009928	Organ Specificity	Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.	Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D002147	Calmodulin	A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.	Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent
D002148	Calmodulin-Binding Proteins	Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.	Caldesmon,Calspectin,CaM-BP(80),Caldesmon (77),Calmodulin Binding Proteins,Proteins, Calmodulin-Binding
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D003345	Corticosterone	An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)
D004591	Electrophoresis, Polyacrylamide Gel	Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.	Polyacrylamide Gel Electrophoresis,SDS-PAGE,Sodium Dodecyl Sulfate-PAGE,Gel Electrophoresis, Polyacrylamide,SDS PAGE,Sodium Dodecyl Sulfate PAGE,Sodium Dodecyl Sulfate-PAGEs