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)

Retro-orbital tissue membranes have been shown to have adenylate cyclase activity which can be stimulated by thyrotropin and by an exophthalmogenic factor derived from the thyrotropin molecule by partial pepsin digestion. This stimulable activity is maximal after 15 min and is optimal in the presence of 3 mM magnesium and 1.5 mM ATP. Calcium salts are exquisitely inhibitory to the hormonal stimulation; sodium, lithium, and ammonium salts are significantly less inhibitory. Thyrotropin and the exophthalmogenic factor induce similar maximal levels of stimulation but a 4- to 5-fold higher concentration of exophthalmogenic factor is required to achieve this level. Fluoride stimulates adenylate cyclase activity 2- to 3-fold higher than either thyrotropin or the exophthalmogenic factor; thyrotropin, luteinizing hormone, the beta subunit of thyrotropin, and the alpha subunit of thyrotropin have relative activities for stimulation of cyclase activity of 100:2:2 less than 0.5. Several other polypeptide and glycoprotein hormones have no effect. The gamma-globulin from patients with malignant exophthalmos has no significant effect on cyclase activity either alone or in the presence of maximal levels of thyrotropin or the exophthalmogenic factor; this gamma-globulin does, however, stimulate cyclase activity at submaximal hormone levels. Trypsin not only destroys the hormone-stimulable adenylate cyclase activity on retro-orbital tissue plasma membranes, but also destroys it on the 15,000 to 30,000 molecular weight receptor fragment released from the membranes by the tryptic action.
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PMID:Stimulation of adenylate cyclase activity in retro-orbital tissue membranes by thyrotropin and an exophthalmogenic factor derived from thyrotropin. 5 Oct 22

Some effects of salts on the adenylate cyclase of partially purified plasma membranes from rat liver have been studied. Under conditions where cyclic adenosine 3':5'-monophosphate formation was linear with respect to time and protein concentration, the enzyme was stimulated 3- to 6-fold by 10 mM NaF, 10- to 30-fold by 1 muM glucagon, 4- to 5-fold by 0.1 mM 5'-guanylylimidodiphosphate, and in the presence of 3 muM GTP, 2-fold by 10 mug/ml of prostaglandin E1. Various salts were found to stimulate basal activity slightly, but enhanced the response to NaF 3- to 4-fold, to glucagon 1.5- to 2-fold, to 5'-guanylylimidodiphosphate 2- to 3-fold, and to prostaglandin E1 1.5-fold. This enhancement was observed at maximally effective concentrations of each of the respective activators. Of the salts tested, NaN3 and the Na- or K-halides were most effective. Their action appeared to be due to the respective anions. Stimulation was detectable with 1.5 mM NaN3 or 3 mM NaCl and was maximal with 30 mM NaN3 or 60 mM NaCl. The stimulatory effect of NaN3 was not due to ATP-sparing, nor to an altered cyclic adenosine 3':5'-monophosphate recovery. It was independent of the chromatography and assay methods used, and was therefore not due to procedural artifact. Fluoride-stimulated cyclase activity was enhanced by salts to a greater degree than were 5'-guanylylimidodiphosphate-, glucagon-, or (prostaglandin E1 + GTP)-stimulated activities. The effects of NaN3 were not the result of significant changes in the enzyme's responses to GTP, which increased basal and glucagon-stimulated activities but inhibited F--stimulated activity. The effects of NaN3 were greater when cyclase was assayed with Mn2+ than with Mg2+. The facilitatory effect of NaN3 or NaCl on fluoride-stimulated adenylate cyclase activity was partially reversible as was the stimulatory effect of fluoride in the presence of NaN3. Enhancement of hormonal stimulation by NaN3 was also demonstrable with cardiac and adipose tissue adenylate cyclase. However, NaN3 did not stimulate detergent-dispersed adenylate cyclases from either liver plasma membranes or brain. The data suggest that stimulation of adenylate cyclase by salts may require the added presence of other stimulatory agents and an intact membrane structure.
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PMID:Liver membrane adenylate cyclase. Synergistic effects of anions on fluoride, glucagon, and guanyl nucleotide stimulation. 12 55

In order to compare the known morphological changes which occur during the postnatal development of the salivary glands in the rat with alterations in membrane function, we measured adenylate cyclase activity and its responses to sodium fluoride (NaF), norepinephrine, and isoproterenol in salivary gland membranes at various times after birth. In the parotid gland, basal enzyme activity did not change significantly during postnatal life, but fluoride-stimulated activity rose on day 15; A similar marked rise in activity stimulated by norepinephrine (0.02 mM) and isoproterenol (0.03 mM) was noted simultaneously. In the submandibular gland, basal adenylate cyclase activity was higher just after birth than at 25 days of life or in maturity. Fluoride-stimulated activity was 7 times higher than basal activity on day 1, greater than 10 times higher on day 25, and 30 times greater in the adult. The gland was as responsive to norepinephrine and isoproterenol on day 5 as it was on day 25 or in the mature animal, showing a two- to threefold increase over the basal enzyme value at each time point studied. Residual phosphodiesterase activity in the membranes was always negligible. The data demonstrate a time-dependent developmental change in the responsiveness of the parotid gland to norepinephrine and isoproterenol, which corresponds to the time when morphological maturation normally occurs. By contrast, in the submandibular gland, membrane-bound adenylate cyclase is fully developed at the time of birth.
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PMID:Postnatal development of adenylate cyclase in rat salivary glands: patterns of hormonal sensitivity. 16 27

The present study was initiated to determine whether specific hormones would influence adenylate cyclase activity within the maxillary-palatal complex during formation of the hamster secondary palate. Stages from initial appearance of the palatal processes to shortly after birth were studied. Highest basal adenylate cyclase activities occurred during the earliest periods of palate development. This basal enzyme activity began to diminish as palatal fusion occurred and remained lowered until birth. Activation of adenylate cyclase by fluoride was maximal at concentrations of 5-10 mM, and was observed throughout the span of palatal development. Fluoride activation of adenylate cyclase was greatest prior to fusion of the palatal processes, then decreased until birth when a slightly increased enzymatic stimulation was seen. Norepinephrine and epinphrine were the catecholamines most capable of inducing increased activation of adenylate cyclase at most periods of palatal growth. Increased enzyme activity in the presence of norepinephrine was more susceptible to antagonism by the beta adrenergic agent, propranolol, than to the alpha adrenergic agent, phentolamine. The remaining catecholamines, namely isoproterenol and dopamine, displayed a lesser ability to activate the enzyme, and adenylate cyclase was not equally responsive to these catecholamines at identical developmental stages. Other hormones, i.e. histamine, serotonin, thyrotropin, growth hormone, thyroxine and glucagon were generally ineffective in activating the enzyme. Phosphodiesterase activity was not detected until shortly before birth.
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PMID:Catecholamine-sensitive adenylate cyclase in the developing golden hamster palate. 17 49

Incubation (30 degrees) of fat cell particulate fractions with fluoride before assay in the effective absence of fluoride results in activation of adenylate cyclase. Whereas the effect of fluoride (1.3 to 7 mM) when added to the assay was maximal in less than 2 min, 10 or 15 min of incubation before assay was usually required to produce maximal activation with any given concentration of fluoride. Under both conditions 3 to 5 mM fluoride produced maximal activation. After incubation with fluoride for 5 to 20 min cyclase activity was constant for at least 15 min of assay without fluoride; maximal activity was greater than that produced by fluoride added to the assay system and the concentration required to produce significant activation was lower. Fluoride activation in the assay or during prior incubation could be prevented by pyrophosphate. When added during the early minutes of assays with fluoride, 1.5 mM pyrophosphate, which had little effect on the activity of enzyme previously incubated with fluoride, rapidly reduced activity to essentially basal levels; when added after 10 min its effect was equally rapid but much smaller. It appears that activation is initially reversible by removal of fluoride as it is by addition of pyrophosphate, but becomes largely irreversible by these means with continued exposure to fluoride. Fluoride in the assay system inhibited cyclase activated by isoproterenol or choleragen or by incubation with fluoride prior to assay; inhibition, dependent on fluoride concentration, was maximal at 5.3 mM. Since maximal activity produced by incubation with fluoride before assay exceeded that of nonincubated preparations assayed with fluoride, and was reduced to the latter level when assayed in the presence of fluoride, we infer that inhibition is reversible at a time when fluoride activation is relatively irreversible. Pyrophosphate (1.5 mM), which prevented fluoride activation, did not reduce fluoride inhibition of isoproterenol-, fluoride-, or choleragen-activated cyclase. When 3 mM MnCl2 was present in the assay, inhibition by fluoride was not observed. In descriptive terms, MnCl2 appeared to cause rapid reversal of fluoride inhibition. Thus, fluoride inhibits, in an apparently similar manner, fat cell adenylate cyclase whether it is activated by isoproterenol, fluoride, or choleragen. Although fluoride activation and inhibition can apparently be dissociated or modified differentially, until the mechanism(s) of action of fluoride is elucidated it cannot be concluded that these are totally independent processes.
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PMID:Activation and inhibition of fat cell adenylate cyclase by fluoride. 18 6

Incubation of erythrocytes or their isolated membranes with N, N'dicyclohexyl carbodiimide (DCC) blocked isoproterenol activation of the adenylate cyclase. Fluoride activation remained unaffected. L-epinephrine and DL-propranolol partially and transiently protected the system against DCC. D-Epinephrine and dopamine did not protect. The enzyme system preactivated by isoproterenol plus Gpp(NH)p was no longer sensitive to DCC. In contrast to the water insoluble DCC, a water soluble carbodiimide acted only at high concentration and blocked fluoride as well as catecholamine activation of the adenylate cyclase. The findings indicate that DCC attacks a group on, or near, the beta-adrenergic receptor and that this group is located in a hydrophobic region of the cell membrane. It is argued that a low nominal concentration of DCC in the aqueous suspension of erythrocytes actually represents a very high concentration of DCC in the hydrophobic region of the cell membranes, near the beta-adrenergic receptor. The reaction with DCC may prove to be a useful tool in future analyses of beta-adrenergic receptor function.
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PMID:Blocking of catecholamine activation of adenylate cyclase by N, N'dicyclohexyl carbodiimide in turkey erythrocytes. 18 26

The ontogeny of beta-adrenergic receptors in rat cerebral cortex has been studied using [125I]iodohydroxybenzylpindolol as a ligand in an in vitro binding assay. The concentration of beta-adrenergic receptors was very low during the first week after birth. Between days 7 and 14 there was a rapid increase in the density of receptors. Adult levels were reached by the end of the second week. The affinities of 1-isoproterenol and iodohydroxybenzylpindolol for beta-adrenergic receptors did not vary with the age of the animal. Fluoride stimulated adenylate cyclase activity in the cerebral cortex was 40% of the adult level at birth and gradually increased to maximal levels over the next two weeks. On the other hand, catecholamine stimulated cyclic-3',5'-adenosine monophosphate accumulation was barely detectable during the first week after birth, but it increased rapidly to adult levels between days 7 and 14. The results suggest that it is the development of beta-adrenergic receptors that permits the expression of catecholamine sensitive adenylate cyclase activity. Norepinephrine stores in the cerebral cortex developed slowly reaching adult levels approximately two months after birth. There is therefore little correlation between the ontogeny of presynaptic adrenergic nerve terminals and the postsynaptic development of beta-adrenergic receptors.
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PMID:Ontogeny of beta-adrenergic receptors in rat cerebral cortex. 19 17

Fluoride-stimulated adenylate cyclase is demonstrated inisolated tumor cells of transplantable rat pituitary tumor MtT-F4 in vitro. The intracellular cyclic adenosine 3':5'-monophosphate is lowered in the cells incubated in the presence of synthetic somatostatin. Contrary to the findings reported for normal pituitary, however, the immunoreactive growth hormone release does not change when either somatostatin or phosphodiesterase inhibitors are present in the incubation medium. The presence of dibutyryl cyclic adenosine 3':5'-monophosphate (5 mM) in the incubation medium does not change the rate of growth hormone release by isolated tumor cells.
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PMID:Effect of somatostatin on growth hormone release by MtT-F4 rat pituitary tumor in vitro. 19 84

Fat cell ghosts and homogenates of fat cells were used to study the influence of training on the regulatory system for lipolysis in adipose tissue of female rats. A training effect was identified from elevated succinate dehydrogenase activities in the soleus and plantaris muscles. Neither basal nor maximal (NaF-stimulated) adenylate cyclase activities per mg protein of fat cell ghosts were altered by training. Fluoride-stimulated adenylate cyclase activity per microgram DNA was lower in the trained than untrained group. Adenylate cyclase activities in response to norepinephrine expressed either on a per mg protein or per microgram DNA basis were lower (P less than 0.05) in fat cell ghosts from trained rats. Phosphodiesterase activity was higher (P less than 0.05) in fat cell ghosts from trained rats for cyclic AMP concentrations of 1--5.0 micrometer. The apparent Km's of phosphodiesterase were 1.19 and 2.0 micrometer of cyclic AMP for the untrained and trained groups, respectively (P less than 0.05). Protein kinase activity in the supernatant fraction of homogenates of fat cells was unchanged due to training. The overall effect of training was to blunt the system for cyclic AMP production in rat adipocytes. This may explain, at least partially, the lower plasma free fatty acid levels observed in trained compared to untrained persons during submaximal exercise.
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PMID:Effect of physical training on control mechanisms of lipolysis in rat fat cell ghosts. 19 25

Plasma membranes were prepared from homogenates of two well differentiated hepatomas (Morris rat 7787 and Dalton mouse 9815), two poorly differentiated hepatomas (Morris rat 7288-C and Dalton mouse 129), and normal liver. Adenylate cyclase activity and [125I]iodoglucagon binding were measured in the plasma membrane preparations over a wide range of glucagon concentrations. Nether glucagon-stimulated adenylate cyclase activity nor [125I]iodoglucagon binding could be detected in the poorly differentiated hepatomas. Fluoride and epinephrine stimulated adenylate cyclase activity in all hepatomas. Maximum activity of glucagon-stimulated adenylate cyclase and maximum binding of glucagon in the wall differentiated hepatomas were less than those of normal liver. Plasma membranes from liver and hepatomas were solubilized with Lubrol-PX and, after reducing the concentration of detergent, were incubated with [125I]iodoglucagon and then chromatographed on a column of Bio-Gel A 1,5 m. Two peaks containing both protein and [125I]iodoglucagon were found for normal liver but not for the poorly differentiated hepatomas. Fractions from the Bio-Gel column containing the greatest concentration of protein were also subjected to a binding microassay. Material from the poorly differentiated tumors did not bind glucagon in this system, whereas the solubilized normal liver membranes bound up to 1.4 pmol [125I]iodoglucagon/mg protein. This indicates that there is no detectable glucagon receptor in these undifferentiated tumors.
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PMID:Membrane receptor function and the loss of glucagon-stimulated adenylate cyclase activity in hepatomas. 21 18


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