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)

We examined the effects of synthetic human atrial natriuretic factor (human ANF 99-126) on adenylate cyclase activity, cAMP and cyclic GMP (cGMP) levels, bone resorption, collagen and DNA synthesis, and prostaglandin E2 (PGE2) production in fetal rat bone organ cultures. ANF (100 nM) inhibited PTH- and PGE2-stimulated cAMP production but had no effect on basal cAMP production in 21-day fetal rat calvaria. ANF increased cGMP levels, and this was not affected by PTH. ANF (10 nM) partially inhibited bone resorption stimulated by PGE2 but had no effect on control or PTH-stimulated resorption in 19-day fetal rat long bones. ANF had no effect on collagen and DNA synthesis or PGE2 production and did not alter responses to PTH or PGE2 in the fetal rat calvaria. Thus, ANF has no major direct effect on bone resorption or formation, but it is possible that ANF modulates the local regulatory function of PGE2 in bone.
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PMID:Effects of atrial natriuretic factor on cyclic nucleotides, bone resorption, collagen and deoxyribonucleic acid synthesis, and prostaglandin E2 production in fetal rat bone cultures. 255 55

The sequence of atrial natriuretic factor (ANF) has been determined, as well as the complete structure of the rat and human complementary DNA and gene. ANF and ANF messenger RNA are present not only in atria but also in ventricles. The circulating form of ANF has been identified as the C-terminal of the molecule, ANF (Ser 99-Tyr 126). The isolated secretory granules of rat atrial cardiocytes contain only pro-ANF (Asn 1-Tyr 126). An enzyme (IRCM-SP1) has been isolated from heart atria and ventricles. This enzyme is highly specific in cleaving ANF (Asn 1-Tyr 126), to yield ANF (103-126), (102-126), and (99-126). In target cells, ANF produces a rise in cyclic guanosine 3',5'-monophosphate (cGMP) due to activation of particulate guanylate cyclase, and inhibition of adenylate cyclase leading in some cases to a decrease in cyclic adenosine 3',5'-monophosphate (cAMP). ANF produces relaxation of rabbit and rat aortic strips, inhibits steroidogenesis in both zona glomerulosa and zona fasciculata cells, and inhibits the release of arginine vasopressin from the isolated rat hypothalamohypophysial preparation in vitro but decreases AVP release in vivo only at pharmacological doses. In all forms of experimental hypertension, plasma levels of ANF are increased and, at some time periods, atrial levels are also decreased. The ventricular levels of immunoreactive ANF are also increased in renal hypertension. Infusion of ANF by minipumps decreases the blood pressure near control levels in several models of experimental hypertension. In cardiomyopathic hamsters with heart failure, the atrial levels of immunoreactive ANF are decreased while the plasma and ventricular levels are increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The heart as an endocrine gland. 282 60

We examined the effects of several in vitro experimental systems on the apparent potencies of putative secretagogues for stimulating ACTH release from rat anterior pituitary cells. Cells were prepared by trypsin digestion and gentle mechanical dispersion. Aliquots of the same cell preparations were tested in 1) a microperifusion system immediately after dispersion (day 0), 2) the same microperifusion system after 4 days of static suspension culture on a layer of Sephadex G-10 gel particles (day 4), 3) a static suspension system after 4 days of static suspension culture, and 4) a static monolayer system after 4 days of monolayer culture. Ovine CRF stimulated release of similar amounts of ACTH in all of the systems on days 0 and 4, except in one experiment, in which the response was less on day 4. Arginine vasopressin (AVP), oxytocin, and angiotensin II all appeared to be more potent in day 4 than in day 0 cells in the perifusion system, and the synergism of AVP with ovine CRF was also increased. Dioctanoylglycerol, which directly activates protein kinase-C, and forskolin, which directly activates adenylate cyclase, both stimulated greater release in day 4 cells. The mechanism(s) responsible for the difference in the responses of day 0 and day 4 cells is unknown. Epinephrine had only a small effect in the microperifusion system, but both epinephrine and norepinephrine had potencies comparable to AVP in the static suspension and monolayer systems. This was not due to prolonged exposure to the catecholamines, suggesting that these agents may act on other anterior pituitary cells to release metabolic products that secondarily stimulate the corticotrophs to release ACTH. The same situation appears to be true for atrial natriuretic factor. Gastrin-releasing peptide, its bioactive COOH-terminal half, which was active in a rat urinary bladder smooth muscle assay, its amphibian analog, bombesin, and cholecystokinin (26-33) were devoid of ACTH-releasing activity in all of the systems, in contrast to the findings of others. Since 4-day culture of dispersed cells improved most of their responses and diminished none, we postulate that they may more closely resemble normal pituitary cells in function, and since cellular metabolites are unlikely to accumulate in the interstitial fluid of the pituitary gland, we propose that the secretory functions of cells in perifusion systems may more closely resemble those in the pituitary gland in situ than they do in static incubation systems.
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PMID:Effects of several in vitro systems on the potencies of putative adrenocorticotropin secretagogues on rat anterior pituitary cells. 283 88

In the presence of 1 microM atrial natriuretic factor (ANF) and low (0.1 mM) Mg2+ concentrations, the initial rate of binding of [3H]guanosine 5'-[beta, gamma-imido)triphosphate [( 3H]p[NH]ppG) to rat lung plasma membranes was increased twofold to threefold. ANF-dependent stimulation of the initial rate of [3H]p[NH]ppG binding was reduced at high (5 mM) Mg2+ concentrations. Preincubation of membranes with p[NH]ppG (5 min at 37 degrees C) eliminated the ANF-dependent effect on [3H]p[NH]ppG binding whereas ANF-dependent [3H]p[NH]ppG binding was unaffected by similar pretreatment with guanosine 5'-[beta-thio]diphosphate (GDP[beta S]). An increase in ANF concentration from 10 pM to 1 microM caused a 40% decrease in forskolin-stimulated or isoproterenol-stimulated adenylate cyclase activities (IC50 5 nM) in rat lung plasma membranes. GTP (100 microM) was obligatory for the ANF-dependent inhibition of adenylate cyclase, which could be completely overcome by the presence of 100 microM GDP[beta S] or the addition of 10 mM Mn2+. Reduction of Na2+ concentration from 120 mM to 20 mM had the same effect. Pertussis toxin eliminated ANF-dependent inhibition of adenylate cyclase by catalyzing ADP-ribosylation of membrane-bound Ni protein (41-kDa alpha subunit of the inhibitory guanyl-nucleotide-binding protein of adenylate cyclase). The data support the notion that one of the ANF receptors in rat lung plasma membranes is negatively coupled to a hormone-sensitive adenylate cyclase complex via the GTP-binding Ni protein.
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PMID:Involvement of Ni protein in the functional coupling of the atrial natriuretic factor (ANF) receptor to adenylate cyclase in rat lung plasma membranes. 283 33

In the membranous signal transduction process, hormone-binding to receptors causes receptor interaction with signal-transducing components; these components transfer the stimulus to effector systems, which generate intracellular signals. Several guanine nucleotide-binding proteins (N- or G-proteins) have been identified as membranous signal-transducing components. Two N-proteins are involved in the hormonal regulation of adenylate cyclase activity, one of which being stimulatory (Ns), the other one being inhibitory (Ni). Ns, Ni and a third N-protein, No, whose function is unknown, occur ubiquitously. On the other hand, transducin, an N-protein, which functionally couples light-activated rhodopsin to a cGMP phosphodiesterase, is specific for the retina. In addition to their established role as transducers regulating adenylate cyclase and retinal cGMP phosphodiesterase, N-proteins proteins may be involved in two mechanisms by which the cytoplasmic calcium concentration is elevated, i.e. hormonal stimulation of a phospholipase C catalyzing phosphatidyl-inositol 4,5-diphosphate hydrolysis (Pi response) and hormone-induced opening of receptor-operated calcium channels; the membrane-bound forms of cAMP phosphodiesterase and guanylate cyclase, stimulated by insulin and atrial natriuretic factor, respectively, are also likely to be regulated via N-proteins. Guanine nucleotide-binding proteins appear to play a universal role in transmembranous signalling processes, controlling effector systems (i.e. enzymes and ion channels) that regulate cytoplasmic concentrations of intracellular messengers such as cyclic AMP, cyclic GMP and calcium.
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PMID:[Principles of transmembranous signal transduction in the action of hormones and neurotransmitters]. 286 63

Atrial natriuretic factor (ANF) acts through specific receptors at its target tissues. Receptor-occupancy by ANF induces activation of particulate guanylate cyclase, increased cyclic GMP formation and also inhibition of adenylate cyclase which results in a decrease of cyclic AMP formation. These second messenger systems appear to mediate the effects of ANF in target tissues. Following receptor-mediated activation of particulate guanylate cyclase, cyclic GMP is extruded from the cells, which leads to elevated cyclic GMP levels in plasma and urine in man, whereas cyclic AMP levels remain unchanged. Since cyclic GMP has a much longer half-life than ANF, it is more sensitive as a marker for ANF release than ANF itself, which has a half-life of just a few minutes. Since cyclic GMP is excreted into urine, determinations of urine cyclic GMP can also allow conclusions about the ANF system when blood sampling is impractical. Thus, cyclic GMP and not cyclic AMP is a sensitive biological marker for ANF.
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PMID:Mechanisms of action of atrial natriuretic factor: clinical consequences. 287 64

Human prepro atrial natriuretic factors 26-55, 56-92, and 104-123 as well as human atrial natriuretic factor (4-28) in the present investigation increased renal cortical and medullary cyclic GMP levels and maximally enhanced particulate guanylate cyclase activity [E.C. 4.6.1.2] two-fold in whole kidney homogenates, renal cortical and medullary membranes, and in isolated distal nephrons at their 1 microM concentrations. Dose-response relationships revealed that the half maximal [ED50] activation of guanylate cyclase was at their 10 nM concentrations in rat, rabbit, and dog kidneys. Both human atrial natriuretic factor and the prepro factors decreased adenylate cyclase activity. These results suggest that prepro factors 26-55, 56-92, 104-123 may also be functionally active.
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PMID:Human prepro atrial natriuretic factors 26-55, 56-92, and 104-123 increase renal guanylate cyclase activity. 288 43

Atrial natriuretic factor (ANF) interacts with its target cells through specific receptors. This interaction induces, in most cell types, the activation of particulate guanylate cyclase and decreased Calcium mobilisation. In addition, ANF also decreases adenylate cyclase activity in some tissues. Activation of particulate guanylate cyclase, and additionally inhibition of adenylate cyclase, appear to initiate the cellular responses to circulating ANF. The activation of particulate guanylate cyclase is tissue-specific, immediate and can be demonstrated also on the solubilized enzyme. The ANF receptor appears to be tightly coupled to particulate guanylate cyclase. The increased formation of cyclic GMP induces cGMP-dependent protein phosphorylation in target cells. In addition, cyclic GMP inhibits Calcium mobilisation in several tissues. This may explain observations of inhibition of Calcium mobilisation after ANF. Cyclic GMP is not only degraded by phosphodiesterase, but is also extruded from target cells. As a consequence of cGMP extrusion, ANF increases the levels of cyclic GMP in plasma and urine in animals and man. Cyclic GMP is also increased in various disease states, in which ANF is increased. In contrast, cyclic AMP plasma levels are unaltered after ANF elevations. At present, the exact mechanisms, by which cellular functions are altered by ANF are still incompletely understood. It is anticipated, that the close correlation between the cyclic GMP system and effects of ANF in various target tissues is a key finding that will help elucidate the exact mechanisms of ANF action.
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PMID:Cellular mechanisms of action of atrial natriuretic factor. 288 40

The present investigation was designed to determine if atrial natriuretic factor relaxes non-vascular smooth muscle. Rather than cause a relaxation, atrial natriuretic factor induced a two-to-four fold enhancement in the amplitude of the spontaneous phasic contractions of duodenal longitudinal muscle. Dose-response curves revealed that ANF enhanced these contractions over a concentration range of 10 picomoles to 100 nanomoles with the ED50 at 1 nanomolar. The increased amplitude of contraction began within 30 seconds and was calcium-dependent. The increased force of contraction was associated with a three-fold increase in cyclic GMP levels and activation of particulate guanylate cyclase [E.C.4.5.1.2.]. Atrial natriuretic factor had its half-maximal [ED50] activation of guanylate cyclase at its 1 nM concentration while maximal enhancement was at its 100 nM concentration in duodenum, jejunum, and ileum. Atrial natriuretic factor did not stimulate adenylate cyclase [E.C.4.6.1.1.]. Thus, atrial natriuretic factor increases the force of the spontaneous phasic contractions of the small intestine which are calcium-dependent and associated with activation of the guanylate cyclase-cyclic GMP system.
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PMID:Atrial natriuretic factor increases the magnitude of duodenal spontaneous phasic contractions. 290 55

alpha 2-adrenergic receptor-mediated signal transduction in rat adrenocortical carcinoma cells occurs through the opposing regulation of two second messengers, cyclic GMP and cyclic AMP, in which guanylate cyclase is coupled positively and adenylate cyclase negatively to the receptor signal. We now show that in these cells phorbol 12-myristate 13-acetate (PMA), a known activator of protein kinase C, inhibits the alpha 2-agonist (p-aminoclodine)-dependent production of cyclic GMP in a dose-dependent and time-dependent fashion. The half-maximal inhibitory concentration of PMA was 10(-10) M. A protein kinase C inhibitor, 1-(5-isoquinolinyl-sulfonyl)-2-methyl piperazine (H-7), caused the release of the PMA-dependent attenuation of p-aminoclodine-stimulated cyclic GMP formation. These results suggest that protein kinase C negatively regulates the alpha 2-receptor coupled cyclic GMP system in these cells, a feature apparently shared with the other cyclic GMP-coupled receptors such as those of muscarine, histamine, and atrial natriuretic factor.
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PMID:Inhibition of alpha 2-adrenergic receptor-mediated cyclic GMP formation by a phorbol ester, a protein kinase C activator. 290 36


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