Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stereotaxic injection of 2.5 microng of kainic acid, a rigid analogue of glutamate into the rat striatum caused a 70% reduction in the striatum of the cholinergic parameters, choline acetyltransferase, acetylcholine and synaptosomal uptake of choline and a similar reduction in the GABAergic parameters, glutamic acid decarboxylase, psi-aminobutyric acid (GABA) and synaptosomal uptake of GABA. In contrast, the striatal content of dopamine and the synaptosomal uptake of dopamine were unchanged, and the activity of tyrosine hydroxylase was significantly increased. Significant changes in the activity of neurotransmitter synthesizing enzymes were demonstrable within 6h after injection of 2.5 microng of kainic acid and maximal effects occurred at 48h; the activities of choline acetyltransferase and glutamic acid decarboxylase remained depressed up to 21 days after injection. The kinetic characteristics of striatal tyrosine hydroxylase were altered 48h after injection with a two-fold increase in the Vmax for tyrosine and a three-fold reduction in Km for the pteridine cofactor. In contrast to the effects of kainic acid, the injection of copper sulfate, a non-specific toxin, caused a proportionate reduction in the dopaminergic as well as the cholinergic and GABAergic presynaptic markers. The kainate lesion caused an 85% decrement in the activity of dopamine-sensitive adenylate cyclase, a 40% reduction in the specific binding of [3H]quinuclidinyl benzilate and a 195% increase in the specific binding of [3H]GABA in the striatum. The morphology of the kainate injected striatum was markedly altered with nearly a complete loss of intrinsic neurons, increased number of glial cells but intact internal capsule fibers. Intracerebral injection of nanomolar quantities of kainic acid appears to cause degeneration of neurons with cell bodies near the injection site while sparing axons terminating in or passing through the region.
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PMID:Striatal lesions with kainic acid: neurochemical characteristics. 1 86

Rabbit liver adenylyl (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) cyclase was stimulated by preincubation with F- and Mg2+ and the stimulation persisted despite extensive washing and/or detergent solubilization. Optimum preactivation conditions were found to be 4 mM NaF and 2 mM MgCl2; higher or lower concentrations produced submaximum stimulation regardless of preincub ation time. In addition to an enhanced catalytic acticity, the activated enzyme also exhibited different responses to Ca2+ and Cu2+ when compared to the basal enzyme. ATP caused a time-dependent inhibition that could be partially prevented or reversed by F-, but was not completely reversed by washing. This inhibition was not observed when 5'-adenosine(beta, gamma-imide) triphosphate blocks inhibition by ATP. The results support, but do not prove, the proposed molecular basis of F- activation which entails a phosphorylation-dephosphorylation mechanism.
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PMID:Studies of fluoride-preactivated rabbit liver adenylyl cyclase. 68 50

The effect of divalent cations on bovine sperm adenylate cyclase activity was studied. Mn2+, Co2+, Cd2+, Zn2+, Mg2+ and Ca2+ were found to satisfy the divalent cation requirement for catalysis of the bovine sperm adenylate cyclase. These divalent cations in excess of the amount necessary for the formation of the metal-ATP substrate complex were found to stimulate the enzyme activity to various degrees. The magnitude of stimulation at saturating concentrations of the divalent cations was strikingly greater with M2+ than with either Ca2+, Mg2+, Zn2+, Cd2+ or Co2+. The apparent Km was lowest for Zm2+ (0.1 - 0.2 mM) than for any of the other divalent cations tested (1.2 - 2.3 mM). The enzyme stimulation by Mn2+ was decreased by the simultaneous addition of Co2+, Cd2+, Ni2+ and particularly Zn2+ and Cu2+. The antagonism between Mn2+ and Cu2+ or Zn2+ appeared to have both competitive and non-competitive features. The inhibitory effect of Cu2+ on Mn2+-stimulated adenylate cyclase activity was prevented by 2,3-dimercaptopropanol, but not by dithiothreitol, L-ergothioneine, EDTA, EGTA or D-penicillamine. Ca2+ at concentrations of 1-5 mM was found to act synergistically with Mg2+, Zn2+, Co2+ and Mn2+ in stimulating sperm adenylate cyclase activity. The Ca2+ augmentation of the stimulatory effect of Zn2+, Co2+, Mg2+ and Mn2+ appeared to be specific.
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PMID:The effect of divalent cations on bovine spermatozoal adenylate cyclase activity. 122 40

A study was made of the effect of copper laser therapy on the content of PGE and PGF2 alpha and on the adenylate cyclase system (cAMP, cGMP and adenylate cyclase content) in patients with gastric ulcer. Seventy patients with indolent (from 3 months to 2 years) gastric ulcers were examined. The patients were assigned into 2 groups: group I received drug therapy combined with the influence of laser on copper vapours on the ulcerous surface (a single radiation dose 10 to 15 J). As compared to group I, the patients of group II manifested a considerable rise of the content of cAMP and prostaglandins, as well as adenylate cyclase activation in the gastric mucosa. Nonspecific biostimulating action of laser radiation exercised via the influence on the dysregenerative processes in the epitheliocytes of long nonhealing ulcer edges is under discussion.
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PMID:[The effect of laser therapy on the mechanisms for generating healing in long-term nonhealing stomach ulcers]. 233 23

Chloride secretion (Isc) by the opercular epithelium of the teleost, Fundulus heteroclitus, is stimulated by elevations in intracellular cyclic AMP (cAMP) elicited by beta-adrenergic agonists, such as isoproterenol, and is accompanied by a small but significant increase in the transepithelial conductance (Gt). Cupric ions (Cu2+) have been shown to block the apical membrane Cl- channels in this epithelium, leading to a reduction in both the Isc and Gt (Degnan, '85). In the present studies, the effects of Cu2+ on cAMP-elevated and cAMP-depleted epithelia were observed to define the actions of cAMP in this stimulatory process. At a concentration of 5 X 10(-4) M in the mucosal solution, Cu2+ inhibited the Isc 79.8% and reduced the Gt 39.2%. Isoproterenol produced an attenuated stimulation of the Isc in these tissues compared to untreated controls, but had no effect on the Gt. In tissues bathed bilaterally with Cl- -free Ringer, the Isc was virtually abolished and the Gt was reduced 37.0%; neither Cu2+ nor isoproterenol had any effects on the Isc or Gt under this condition. Simultaneous 2 2Na and 3 6 Cl unidirectional flux determinations indicated that the only effects of both isoproterenol and Cu2+ were on the active Cl- secretory flux. An inhibitor of adenylate cyclase, 2',5' dideoxyadenosine (DDA), reduced the Isc and Gt 39.8% and 20.8% respectively. This inhibitor had no additional effects in Cu2+ -treated tissues and the action of Cu2+ on the Gt was reduced in DDA-treated tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic AMP stimulation of Cl- secretion by the opercular epithelium: the apical membrane chloride conductance. 242 33

Sucrose and other saccharides, which produce an appealing taste in rats, were found to significantly stimulate the activity of adenylate cyclase in membranes derived from the anterior-dorsal region of rat tongue. In control membranes derived from either tongue muscle or tongue non-sensory epithelium, the effect of sugars on adenylate cyclase activity was either much smaller or absent. Sucrose enhanced adenylate cyclase activity in a dose-related manner, and this activation was dependent on the presence of guanine nucleotides, suggesting the involvement of a GTP-binding protein ('G-protein'). The activation of adenylate cyclase by various mono- and di-saccharides correlated with their electrophysiological potency. Among non-sugar sweeteners, sodium saccharin activated the enzyme, whereas aspartame and neohesperidin dihydrochalcone did not, in correlation with their sweet-taste effectiveness in the rat. Sucrose activation of the enzyme was partly inhibited by Cu2+ and Zn2+, in agreement with their effect on electrophysiological sweet-taste responses. Our results are consistent with a sweet-taste transduction mechanism involving specific receptors, a guanine-nucleotide-binding protein and the cyclic AMP-generating enzyme adenylate cyclase.
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PMID:Sweet tastants stimulate adenylate cyclase coupled to GTP-binding protein in rat tongue membranes. 250 47

A technique is described, involving tissue dissociation and micro-dissection, for the isolation of interlobular ducts from the pancreas of copper-deficient rats. The average length and outside diameter of the isolated ducts were 589.0 +/- 18.6 and 78.1 +/- 1.6 micron (mean +/- S.E.M., n = 425) respectively. Between twenty and fifty ducts could be obtained from each pancreas. Frequently, the smaller intralobular ducts, which had outside diameters of between 15 and 25 micron, were observed as branches of the interlobular ducts. Light and electron microscopy showed that the isolated ducts were structurally intact, and that the epithelial cells possessed all the typical ultrastructural features of duct cells within the gland of copper-replete rats. The isolated ducts consumed oxygen at a rate of 2.27 +/- 0.55 ml O2/min X 100 g wet weight duct epithelium (n = 6). The concentrations of ATP, ADP and AMP in the ducts were 3.78 +/- 0.81, 0.68 +/- 0.19 and 0.41 +/- 0.13 mmol/l duct epithelium (n = 8) respectively. These data give values for ATP:ADP and ATP:AMP ratios of 5.6:1 and 9.2:1 respectively, and an energy charge of 0.85 +/- 0.01 (n = 8) suggesting that the epithelial cells are healthy and in a stable metabolic state. In the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.67 mM), the basal concentration of cyclic AMP in the isolated ducts was 17.4 +/- 0.7 mumol/l duct epithelium (n = 3). Secretin (0.1 nM-1 microM) caused a dose-related increase in cyclic AMP content up to a maximum of 376.0 +/- 85.3 mumol/l duct epithelium (n = 4). This indicates that the epithelial cells possess secretin receptors, and that these receptors can be functionally linked to adenylate cyclase.
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PMID:Isolation of ducts from the pancreas of copper-deficient rats. 301 21

The adenylate cyclase activity of ram sperm increased on freeze-thawing and the enzyme was stable at 0 degrees C. Its activity was stimulated by Mn2+, Zn2+, Co2+, Mg2+ and Ca2+ in descending order of activity. The enzyme was insensitive to fluoride when Mn2+ concentration was in excess. Mn2+-stimulated enzyme activity was decreased by the simultaneous addition of Co2+, or Cd2+, or Ni2+, and particularly Cu2+. Sulfhydryl compounds (viz. dithiothreitol, glutathione, dithiocarbamate, 2-mercaptoethanol, ergothioneine and cysteine) and chelating agents (viz. D-penicillamine and 8-hydroxyquinoline) were effective, to varying degrees, in overcoming the inhibition by Cu2+. Ca2+ augmented the stimulatory effect of Mg2+, Co2+, Zn2+ and Mn2+ on enzyme activity.
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PMID:Control of ram sperm adenylate cyclase by divalent cations. 327 May 3

We have previously shown that extracellular copper (Cu) amplifies prostaglandin E2 (PGE2) stimulation of LHRH release from explants of the median eminence area (MEA) of adult male rats, and that amplification is a post-PGE2 receptor event involving the adenylate cyclase system. We addressed the question: Is the process of Cu-amplified PGE2 stimulation of LHRH release regulated by ovarian steroids and, if so, is the regulatory steroid estrogen and/or progesterone? Immature female rats (30-32 days old) were ovariectomized and 6 days later treated with a combination of these steroids: E, sc implant of 17 beta-estradiol in a Silastic capsule for 3 days; EEi, E plus im injection of 17 beta-estradiol (2 micrograms/rat) 24 h before killing; and P, either im injection of 0.08 mg/kg progesterone 1 h before killing or 10(-9) M P included in the incubation buffer starting 1 h before Cu/PGE2 exposure. Controls were treated with the vehicle. MEAs were incubated for 5 min with 150 microM Cu, for 15 min with 10 microM PGE2, and then for 45 min with buffer (Cu/PGE2); LHRH release into the medium was measured by RIA. Cu/PGE2-stimulated LHRH release from MEA of intact rats was about 10 times greater than basal release. Ovariectomy led to a 50% reduction in Cu/PGE2-stimulated release [sham, 20.6 +/- 2.0 (mean +/- SE); ovariectomized, 9.4 +/- 1.8], pg/30 mm/MEA; and neither E, EEi, nor P significantly altered this response. In contrast, administration of P to either E- or EEi-primed rats augmented Cu/PGE2 stimulation of LHRH release 3.5-fold (E vs. EP or EEi vs. EEiP); however, P did not augment stimulation of LHRH release by Cu alone or PGE2 alone. Also, inclusion of P in the incubation buffer was as effective as in vivo P in augmenting Cu/PGE2 stimulation of LHRH release from the MEA of EEi-primed rats. On the other hand, in vitro P by itself did not alter LHRH release. These effects of P on the response of the MEA to Cu/PGE2 were not accompanied by a significant increase in the MEA content of LHRH. The process of Cu/PGE2 stimulation of LHRH release is regulated by ovarian steroids, so that ovariectomy leads to a marked reduction of the response of the MEA to Cu/PGE2, and P augments this response in an estrogen-dependent manner. Moreover, it is the secretory process elicited by the combined effects of Cu and PGE2 that is augmented by P.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Progesterone augments copper-prostaglandin E2 stimulation of the release of gonadotropin-releasing hormone from explants of the median eminence of immature female rats: an estrogen-dependent process. 328 77

The aim of this study was to demonstrate histamine-H2 receptors in glomeruli isolated from rat renal cortex and to correlate binding to stimulation by histamine of glomerular cyclic AMP concentration. Binding studies were performed at 10-12 degrees C using [3H]cimetidine as a tracer. Specificity of binding relies on the following: inhibition of [3H]cimetidine binding by the unlabelled drug, other H2-antagonists and agonists in contrast with the very weak inhibitory effects of H1 agonists and antagonists; reversibility of steady-state binding after addition of unlabelled drug; half inhibition of the glomerular cyclic AMP response to histamine at concentrations of cimetidine close to the KD value derived from the binding studies (3 microM); calculated KD value in agreement with the therapeutical concentration of cimetidine and the physiological concentration of histamine. [3H]Cimetidine binding concentration of cimetidine and the physiological concentration of histamine. [3H]Cimetidine binding strikingly increased in the presence of copper chloride (20-300 microM) due to an increase both in number of sites and affinity. However this greater binding did not influence either the inhibitory effect of cimetidine on histamine-induced glomerular cyclic AMP concentration or the stimulatory effect of histamine itself. [3H]Cimetidine binding was temperature-dependent since it progressively diminished from 0 to 37 degrees. This was not due to [3H]cimetidine degradation as shown by thin layer chromatography but rather to a change in drug-receptor interaction at higher temperatures. Glumerular concentration of cyclic AMP increased progressively in the presence of histamine (0.1-1000 microM). This stimulatory effect was markedly inhibited by H2 antagonists. These data demonstrate the presence in rat glomeruli of H2 receptors linked to adenylate cyclase.
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PMID:Histamine H2 receptors in rat renal glomeruli. 628 Jul 28


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