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)

Adrenergic stimulation of the adenylate cyclase (AC)-cAMP-system and 14C-aminopyrine accumulation, an indirect measure of parietal cell H+-production, was studied in a different preparations of gastric mucosal cells. The beta 2-adrenoceptor agonist hexoprenaline activated AC of crude homogenates from the gastric corpus of mouse, rat, guinea-pig, hog, dog and man. In isolated rat gastric cells (20% parietal cells), treated by low power sonication, 10(-8) to 10(-3) mol/l adrenaline and hexoprenaline activated AC equally potently and efficaciously by maximally 170%. Isoprenaline proved to be less effective activating up to 80%. 5.10(-5) mol/l GMP-PNP augmented basal activity 8.5 times and reduced the maximal efficacy. Adrenaline and hexoprenaline activated AC by maximally 120%, isoprenaline by 40%. The potency of adrenaline was 4 times lower, that of hexoprenaline 2 and that of isoprenaline 4 times higher in the presence of GMP-PNP. Adrenergic stimulation was inhibited by the beta-adrenoceptor antagonist propranolol, the effect of alpha-adrenoceptor-blockade by phenoxybenzamine was less pronounced. In fractions with 7-80% of parietal cells, prepared by isopycnic centrifugation with Percoll, adrenaline and hexoprenaline activated AC or hexoprenaline enhanced the cellular levels of cAMP in parietal cell poor and rich fractions. The degree of activation in response to histamine correlated with the number of parietal cells. 14C-Aminopyrine uptake was increasingly stimulated through 10(-8) to 10(-5) mol/l hexoprenaline, maximally by doubling the basal accumulation. 10(-4) mol/l histamine was 8 times more effective. 3.10(-7) mol/l propranolol inhibited the effect of 10(-5) mol/l hexoprenaline by 80%. The data suggest the localization of beta-adrenoceptors (likely beta 2-adrenoceptors) on parietal and other nonidentified gastric cells. At the parietal cell, adrenaline and hexoprenaline initiate activation of AC and hexoprenaline leads to H+-production. The responses are small compared to the effect of histamine. Thus, beta-adrenoceptor agonists exert intrinsic activity in relation to H+-production. Their influence on stimulated secretion of isolated cells remains to be elucidated.
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PMID:Adrenergic stimulation of isolated rat gastric mucosal cells. Effect on adenylate cyclase and 14C-aminopyrine uptake. 712 15

Effect of lisuride, an ergot derivative of isolysergic structure, on dopamine-sensitive adenylate cyclase was studied in the homogenate of rat corpus striatum. Stimulatory action of lisuride, similar to the actions of dopamine and apomorphine, on striatal adenylate cyclase was potentiated significantly by guanosine triphosphate (GTP) and by guanyl-5'-yl imidodiphosphate (GMP-PNP), although with lisuride alone, there was only a slight stimulation. The maximal stimulation attained in the presence of GTP corresponded to about 1.4 times the basal rate of cyclic AMP formation in the homogenate and was abolished by an addition of haloperidol. Lisuride at a concentration about 3 microM inhibited stimulation of cyclic AMP formation by dopamine. The effect of lisuride and the extent of potentiation by the guanyl nucleotides were almost comparable to the effects of apomorphine, under corresponding conditions. Thus, lisuride, like apomorphine, acts as a partial agonist-antagonist, and has the ability to stimulate the dopamine-sensitive adenylate cyclase in the rat corpus striatum.
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PMID:Stimulatory action of lisuride on dopamine-sensitive adenylate cyclase in the rat striatal homogenate. 720 70

The activity of myocardial adenylate cyclase from two age groups (10-11 and 18-19 weeks old, respectively) of male spontaneously hypertensive rats (SHR) and their age-matched normotensive Wistar-Kyoto rats (WKY) was examined. Stimulation of the enzyme by isoproterenol and 5'-guanylyl-imidodiphosphate (GMP-PNP) was decreased for both SHR and WKY at the older age. In addition, decreased sensitivity of the enzyme to NaF was also found for older SHR. Except for showing subsensitivity to isoproterenol, the enzyme from SHR at 10-11 weeks of age was activated by GMP-PNP alone, or in combination with isoproterenol, and NaF to the same extent as that from the same age group of WKY. Stimulation of the enzyme by these activators was considerably lower from SHR than from WKY at 18-19 weeks of age. These data indicate that myocardial adenylate cyclase from SHR initially demonstrates a selective decrease in response to isoproterenol, and then a generalized decrease in sensitivity to various activators at a later hypertensive stage.
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PMID:Age-dependent changes in the myocardial adenylate cyclase of normotensive and spontaneously hypertensive rat. 720

Cytosolic factors in a 50--75% (NH4)2SO4 fraction of the 105 000 x g supernatant of the renal cortex modulated adenylate cyclase activity in membrane preparations enriched in renal tubular cell basal--lateral membranes. The crude factor preparation had no effect on basal activity but it contained components that augmented the stimulated of the enzyme by NaF, parathyroid hormone (PTH), prostaglandin E1 (PGE1), and inhibited the activation of the enzyme by GMP--PNP. The factor(s) potentiating the stimulation by the hormones was partially purified (13-fold) by DEAE-cellulose and Sephadex G-75 chromatography. During purification, the component(s) that increased hormone-stimulated adenylate cyclase was separated from those affecting the activity in the presence of NaF and GMP--PNP. The factor(s) enhanced the PTH- and PGE1-stimulated enzyme at all concentrations of hormone, suggesting that the affinity for the hormone was not affected. The factor(s) was heat-stable. Partial proteolysis with chymotrypsin greatly reduced the ability of the factor(s) to enhance hormonal responsive adenylate cyclase. However, the factor(s) was resistant to trypsin digestion. The effect of the factor was not due to GTP, nor was GTP necessary for its action. Ca2+ was not needed for the enhancing activity of the factor(s). These findings suggest the presence in the cytosol of the kidney cortex of a protein(s) that regulates the response of renal adenylate cyclase to hormones. The relationship between this kidney cytosolic factor and those reported in other tissues remains to be established.
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PMID:Regulation of hormone(PTH and PGE1)-stimulated adenylate cyclase by renal cytosolic factors. 721 2

Ultrastructural localization of adenylate cyclase (AC) activity was investigated in suspensions of unfixed isolated rat thymocytes using a medium containing 0.6 mM 5'-adenylylimidodiphosphate (AMP-PNP) as a substrate, 10 mM MgSO4 as an activator, 5 mM theophylline as an inhibitor of 3' 5'-AMP-phosphodiesterase and 2 mm lead nitrate as a capturing agent. AC activity was demonstrated in plasma membrane, perinuclear space, endoplasmic reticulum, Golgi complex, centriole microtubules and mitochondria. AC was activated with 10(-4) M adrenaline in the presence of 5'-guanylylimido-diphosphate (GMP-PNP) as well as with 10(-2) M NaF. In the cells incubated in a medium devoid of theophylline and containing 5'-AMP instead of AMP-PNP, 5'-nucleotidase activity was observed in the same cell structures as AC activity, Hydrolysis of 5'-AMP in the nucleus was much stronger than that of AMP-PNP. 10 mM NaF markedly inhibited hydrolysis of 5'-AMP in all cell structures. No staining was observed with 2 mM beta -glycerophosphate as a substrate. Incubation of unfixed thymocytes in media containing AMP-PNP, 5'-AMP or p-nitrophenyl phosphate, but not beta -glycerophosphate, induced both in the nucleus and in the cytoplasm in some cells an appearance of a transitory reticular formation consisting of about 303nm thick strands which could penetrate the nuclear envelope and plasma membrane and form connections with adjacent cells. The transitory reticular formation seems to belong to the cytoskeleton and to be involved in cell aggregation.
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PMID:Ultracytochemical localization of adenylate cyclase activity in rat thymocytes. 729 93

Adenylate cyclase from rat hippocampus was separated by electrophoresis in polyacryl amide microgels and stained for enzymatic activity using a new histochemical procedure. This method involves the use of AMP-PNP, aminophylline, dithiotreitole, and Sr2+ as "primary" capture ions, thus fulfilling all the demands for a really specific histochemical incubation medium for the enzyme. The incubation of the gels with this medium resulted in the inhibition of other enzymes, which are capable of splitting AMP-PNP (ATP: pyrophosphatase, alkaline phosphatase), whereas adenylate cyclase remained highly active under these conditions. The enzyme was found to be present in two forms in the gels. Both protein bands were stimulated by the addition of various biogenic amines to the incubation medium. One protein band was fully GMP-PNP dependent in its activity. It is reasonable to suppose that these forms are either differently high aggregated molecules of the enzyme or enzyme molecules bound to their regulatory sites.
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PMID:Specific demonstration of rat brain adenylate cyclase in polyacryl amide microgels by a new histochemical procedure. 732 48

In G protein-coupled receptors, neurotransmitter-induced binding of GTP to G proteins triggers the activation of effector systems while simultaneously decreasing the affinity of the transmitter for its specific binding site within the receptor-G protein complex. In the present study we show that, in the chick optic tectum, guanine nucleotides inhibit the binding of the glutamate analog, kainate, and activate adenylate cyclase by different mechanisms and acting on different sites. GMP-PNP, a non-hydrolyzable analog of GTP, binds tightly to G proteins so that the binding is stable even after exhaustive washing. By use of this property, we have prepared membrane samples in which G protein GTP-binding sites are pre-saturated with GMP-PNP. Experiments carried out with these membranes show that GMP-PNP, GDP-S and GMP inhibit the binding of [3H]kainate by interacting with site(s) unrelated to G proteins, whereas GMP-PNP activates adenylate cyclase activity by binding to G proteins.
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PMID:Differential effects of guanine nucleotides on kainic acid binding and on adenylate cyclase activity in chick optic tectum. 798 2

The effect of L-pyroglutamic acid, a metabolite that accumulates in pyroglutamic aciduria, on different neurochemical parameters was investigated in adult male Wistar rats. Glutamate binding, adenylate cyclase activity and G protein coupling to adenylate cyclase were assayed in the presence of the acid. L-pyroglutamic acid decreased Na(+)-dependent and Na(+)-independent glutamate binding. Basal and GMP-PNP stimulated adenylate cyclase activity were not affected by the acid. Furthermore, rats received unilateral intrastriatal injections of 10-300 nmol of buffered L-pyroglutamic acid. Vehicle (0.25 M Tris-Cl, pH 7.35-7.4) was injected into the contralateral striatum. Neurotoxic damage was assessed seven days after the injection by histological examination and by weighing both cerebral hemispheres. No difference in histology or weight could be identified between hemispheres. These results suggest that, although capable of interfering with glutamate binding, pyroglutamate did not cause a major lesion in the present model of neurotoxicity.
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PMID:Neurochemical effects of L-pyroglutamic acid. 878 5

An ethnopharmacological survey showed that home remedies prepared with flowers and fruits of Psychotria colorata are used by Amazonian peasants as pain killers. Psychopharmacological in vivo evaluation of alkaloids obtained from leaves and flowers of this species showed a marked dose-dependent naloxone-reversible analgesic activity, therefore suggesting an opioid-like pharmacological profile. This paper reports an inhibitory effect of P. colorata flower alkaloids on [3H]naloxone binding in rat striata as well as a decrease in adenylate cyclase basal activity. The alkaloids did not affect [3H] GMP-PNP binding. These findings provide a neurochemical basis for the opioid-like activity previously detected in vivo and point to Psychotria alkaloids as a potential source of new bioactive opiate derivatives.
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PMID:Effects of Psychotria colorata alkaloids in brain opioid system. 883 29

Bovine adrenal zona fasciculata (AZF) cells express a noninactivating K+ current (IAC) that is inhibited by adrenocorticotropic hormone (ACTH) at picomolar concentrations. Inhibition of IAC may be a critical step in depolarization-dependent Ca2+ entry leading to cortisol secretion. In whole-cell patch clamp recordings from AZF cells, we have characterized properties of IAC and the signalling pathway by which ACTH inhibits this current. IAC was identified as a voltage-gated, outwardly rectifying, K(+)-selective current whose inhibition by ACTH required activation of a pertussis toxin-insensitive GTP binding protein. IAC was selectively inhibited by the cAMP analogue 8-(4-chlorophenylthio)-adenosine 3':5'-cyclic monophosphate (8-pcpt-cAMP) with an IC50 of 160 microM. The adenylate cyclase activator forskolin (2.5 microM) also reduced IAC by 92 +/- 4.7%. Inhibition of IAC by ACTH, 8-pcpt-cAMP and forskolin was not prevented by the cAMP-dependent protein kinase inhibitors H-89 (5 microM), cAMP-dependent protein kinase inhibitor peptide (PKI[5-24]) (2 microM), (Rp)-cAMPS (500 microM), or by the nonspecific protein kinase inhibitor staurosporine (100 nM) applied externally or intracellularly through the patch pipette. At the same concentrations, these kinase inhibitors abolished 8-pcpt-cAMP-stimulated A-kinase activity in AZF cell extracts. In intact AZF cells, 8-pcpt-cAMP activated A-kinase with an EC50 of 77 nM, a concentration 2,000-fold lower than that inhibiting IAC half maximally. The active catalytic subunit of A-kinase applied intracellularly through the recording pipette failed to alter functional expression of IAC. The inhibition of IAC by ACTH and 8-pcpt-cAMP was eliminated by substituting the nonhydrolyzable ATP analogue AMP-PNP for ATP in the pipette solution. Penfluridol, an antagonist of T-type Ca2+ channels inhibited 8-pcpt-cAMP-induced cortisol secretion with an IC50 of 0.33 microM, a concentration that effectively blocks Ca2+ channel in these cells. These results demonstrate that IAC is a K(+)-selective current whose gating is controlled by an unusual combination of metabolic factors and membrane voltage. IAC may be the first example of an ionic current that is inhibited by cAMP through an A-kinase-independent mechanism. The A-kinase-independent inhibition of IAC by ACTH and cAMP through a mechanism requiring ATP hydrolysis appears to be a unique form of channel modulation. These findings suggest a model for cortisol secretion wherein cAMP combines with two separate effectors to activate parallel steroidogenic signalling pathways. These include the traditional A-kinase-dependent signalling cascade and a novel pathway wherein cAMP binding to IAC K+ channels leads to membrane depolarization and Ca2+ entry. The simultaneous activation of A-kinase- and Ca(2+)-dependent pathways produces the full steroidogenic response.
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PMID:Adrenocorticotropic hormone and cAMP inhibit noninactivating K+ current in adrenocortical cells by an A-kinase-independent mechanism requiring ATP hydrolysis. 889 75


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