Adenylate cyclase, in brain

Wojcik, W. J. and Neff, N. H. (1984) Gamma-aminobutyric acid B receptors are negatively coupled to adenylate cyclase in brain and in the cerebellum these receptors may be associated with granule cells. Mol. Pharmacol. 25, 24-28. 

Green, J. P., Johnson, C. L., Weinstein, H., and Maayani, S. (1977) Antagonism of histamine-activated adenylate cyclase in brain by D-lyseigic acid diethylamide. Proc. Natl. Acad. Sci. USA, 74 5697-5701. 

Masana MI, Bitran JA, Hsiao JK, et al In vivo evidence that lithium inactivates Gi modulation of adenylate cyclase in brain. J Neurochem 59 200-205, 1992 Masana MI, Chen G, Shorts L, et al Attenuation of PKC induced cychc AMP increases by chronic lithium an in vivo microdialysis study, (in press)... 

Mork A, Geisler A The effects of lithium in vitro and ex vivo on adenylate cyclase in brain are exerted by distinct mechanisms. Neuropharmacology 28 307-311, 1989c... 

Kodavanti PR S, Mehrotra BD, Cherry SC, et al. 1989c. Inhibition of calmodulin-activated adenylate cyclase in rat brain by selected insecticides. Neurotoxicology 10(2) 219-228. 

Ahn HS, Makman MH. (1979). Interaction of LSD and other hallucinogens with dopamine-sensitive adenylate cyclase in primate brain regional differences. Brain Res. 162(1) 77-88. 

Mork, A. (1993) Actions of lithium on the cyclic AMP signalling system in various regions of the brain—possible relations to its psychotropic actions. A study on the adenylate cyclase in rat cerebral cortex, corpus striatum and hippocampus. Pharmacol Toxicol 73 1 7. 

Ebstein R, Belmaker R, Grunhaus L, et al Lithium inhibition of adrenaline-stimulated adenylate cyclase in humans. Nature 259 411-413, 1976 Ebstein RP, Hermoni M, Belmaker RH The effect of lithium on noradrenahne-in-duced cyclic AMP accumulation in rat brain inhibition after chronic treatment and absence of supersensitivity. J Pharmacol Exp Ther 213 161-167, 1980 Ebstein RP, Lerer B, Shlaufman M, et al The effect of repeated electroconvulsive shock treatment and chronic lithium feeding on the release of norepinephrine from rat cortical vesicular preparations. Cell Mol Neurobiol 3 191-201, 1983 Ebstein RP, Moscovich D, Zeevi S, et al Effect of lithium in vitro and after chronic treatment on human platelet adenylate cyclase activity prosreceptor modification or second messenger signal amplification. Psychiatry Res 21 221-228, 1987 Eccleston D, Cole AJ Calcium-channel blockade and depressive illness. Br J Psychiatry 156 889-891, 1990... 

The 5-HT6 receptors are positively coupled to adenylate cyclase. In the absence of selective agonists and antagonists as well as radioligands, they have been initially localized in the rat brain by Northern blot analyses (218,219), in situ hybridization histochemistry (219-221), and quantitative reverse transcription followed by polymerase chain reaction (222) (see also ref. 210). These studies have established that the receptor mRNA is abundant in extrapyramidal areas such as the striatum, as well as in limbic areas such as the nucleus accumbens, olfactory tubercle, hippocampus, and hypothalamus. 

Clement-Cormier YC, Kebabian JW, Petzold GL, Greengard P (1974) Dopamine-sensitive adenylate cyclase in mammalian brain a possible site of action of antipsychotic drugs. Proc Natl Acad Sci USA 77 1113-1117. 

The assay was used for measuring the activity of adenylate cyclase in microsomes prepared from sea urchin eggs and frozen bovine brain. 

Nijjar, M.S., and Nijjar, S.S. 2000. Domoic acid-induced neurodegeneration resulting in memory loss is mediated by Ca + overload and inhibition of Ca2 + + calmodulin-stimulated adenylate cyclase in rat brain (review). Int J Mol Med 6, 377-389. 

A useful procedure for estimating adenylate cyclase in intact cells and tissues is to incubate the tissue with labelled adenine and then measure the rate of labelling of cyclic AMP [112]. Adenine readily penetrates cells and is partially converted to ATP. In heart slices, the ATP newly synthesised from radioactive adenine was found in equilibrium with the existing pool used for the production of cyclic AMP the specific activity of the newly-formed cyclic AMP was similar in the presence and in the absence of stimulatory hormone [113]. The prelabelling method has been compared with the protein-binding method in brain slices [114,115]. Increases in total levels of cyclic AMP and increases in levels of radioactive cyclic AMP derived from intracellular adenine nucleotides labelled by prior incubation with radioactive adenine occurred on similar time courses and to similar extents. Radioactive cyclic AMP represented a small (7-13%) but relatively constant fraction of the total amount of cyclic AMP. These results provided no evidence for the presence of more than one major compartment of adenine nucleotides in brain slices that serve as a source of nucleotide precursor for cyclic AMP. The nucleotides of this compartment were uniformly labelled by incubation with radioactive adenine [116]. 

Nakaya S, Moss J, Vaughan M (1980) Effects of nucleoside triphosphates on choleragen-activated brain adenylate cyclase. In Biochemistry 19 4871 -4874. 

Premont, J., Dauguet-de Montety, M.-C., Herbet, A., Glowinski, J., Bockaert, J. and Prochiantz, A. (1983) Biogenic amines and adenosine-sensitive adenylate cyclases in primary cultures of striatal neurons. Brain Res. 285 53-61. 

By raising the base level of cAMP and thus increasing the sensitivity of the assay, Florijn et al. (1992) have demonstrated the presence of an ACTH and/or MSH receptor coupled to adenylate cyclase in the brain. The striatum also selects cAMP as a second messenger (Wiegant et al, 1979, 1981 Florijn et al, 1991) but the melanocortins preferentially interact with striatal dopamine D2 receptors (Florijn et al, 1992). 

Adaptation of NE receptors is also observed after long-term administration of other types of drugs. For example, chronic chlorpromazine desensitized cortical NE-sensitive adenylate cyclase in rats 8 but caused supersensitivity in mouse limbic forebrain.70 chronic haloperidol did not desensitize cortical NE-stimulated adenylate cyclase73 but apparently induced up-regulation of a2-adrenoceptors (enhanced locomotor response to clonidine) in mice.87 The methyixanthines (caffeine,88 pentoxyfylline89), which increase turnover of brain NE, caused rapid down-regulation of P-adrenoceptors. 

Forskolin can protect adenylate cyclase In membranes from human platelets, S49 lymphoma cells, and rat brain against thermal denaturatlon, proteolytic Inactivation, and Inactivation with N-ethylmalelmlde (NEM). 3 Solubilized preparations of adenylate cyclase are also protected against thermal denaturatlon by forskolin.These Include preparations which do not contain functional Ns protein. 

Activation of Cyclic AMP Generation in Intact Cells - Forskolin activates adenylate cyclase in Intact cells and tissues with similar characteristics as those observed for activation of the enzyme in membranes and solubilized preparations. These Include preparations of rat35 and human36 adipocytes, human platelets,37 tissue slices from brain and other peripheral tissues,3° and various endocrine and secretory tissues.39 Forskolin stimulates adenylate cyclase in S49 lymphoma cells,25 32 j-at astrocytomas.rat pheochromocytoma cells, 2 cultured pituitary cells, 3-48 cardiomyocytes, >30 cultured leydlg cells,31 and cultured kidney cells.32,53 Forskolin increases intracellular cyclic AMP rapidly with an EC50 of about lOpM, and results in elevations of cyclic AMP over basal levels which range between two and fifty-fold, depending on cell type and tissue. 

Inhibition of forskolln stimulated adenylate cyclase in membranes by guanine nucleotides can be observed when a functional Ni subunit Is present and has been shown in membranes from rat brain,34 s49 lymphoma cells, 28,66 rat adipocytes, and human platelets. This inhibition can be observed with GTP, GppNHp, or GTP-yS (guanosine 5 -(3-0-thlo)triphosphate), is blocked by GDP or GDP-gS (guanosine 5 (2-0-thio)diphosphate), and does not require the presence of an inhibitory hormone. Guanine nucleotide Inhibition of adenylate cyclase is not competitive with forskolln and is not observed when membranes are... 

Adenosine influences adenylyl cyclase activity via an interaction with at least two distinct membrane-associated receptors. The Aj adenosine receptor mediates an inhibition of adenylate cyclase, whereas A receptor activation results in the stimulation of this enzyme (6). These receptor subtypes have been defined further by their structure-activity profiles of agonists (7-9). At Aj adenosine receptors the rank order potency of adenosine analogs is N°-(R-phenylisopropyladenosine (R-PIA) > N -ethylcarboxamidoadenosine (NECA) > 2-chloroadenosine (2-ClA) > S-PIA. In contrast at A2 adenosine receptors the potency series for these agonists is NECA > 2C1A > R-PIA > SPIA (2,2). Adenosine analogs acting on A] receptors have been shown to inhibit adenylyl cyclase in brain tissue. Moreover, the adenosine-induced depression of neuronal activity in the rat hippocampus has been shown to involve an interaction with Ai receptors (10). 

S2, S8). Others have reported that adenosine inhibits adenylate cyclase from brain, adipocytes, and lung tissue (FI, M6, Wl). Brain tissues of most animals have very little adenosine deaminase. In other tissues the role of breakdown products must be further explored. The fact that cyclase in intact slices is stimulated while that of broken-cell preparations is inhibited may be related to the so-called latent adenosine deaminase that is mitochondria-bound and inactive in assays of adenosine deaminase in homogenates (M16). 

Sodium tungstate stimulates production of adenylate cyclase in ovarian homogenates. The activation is rapid and takes place also in brain, heart, lung, kidneys, and liver of the rat. Hwang and Ryan s explanation is based on a phosphate transfer mechanism [19]. 

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