Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid hormone formation requires the coincident presence of peroxidase, H2O2, iodide, and acceptor protein at one anatomic locus in the cell. The peroxidase enzyme appears to be a protoporphyrin lX containing heme protein, with binding sites for both iodide and tyrosine. It is probable that both iodide and tyrosine are oxidized to free radical forms which unite to form iodotyrosine. The peroxidase is also involved through an uncertain mechanism in iodotyrosine coupling and probably in oxidation of sulfhydryl bonds in thyroglobulin. H2O2 may be supplied by microsomal NADPH-cytochrome c reductase or NADH-cytochrome b5 reductase. Other possible intracellular H2OI generating systems include monoamine oxidase and xanthine oxidase. The usual acceptor for iodide is thyroglobulin, which is currently believed to be iodinated within apical secretory vesicles at the cell border just prior to liberation into the colloid, or possibly after liberation into the colloid. Other soluble an insoluble proteins are also iodinated within the gland. The peroxidase is present in numerous cellular structures, but iodination activity occurs primarily, if not only, at the apical cell border. The controls of iodination are imperfectly known. Thyrotrophin modulation of iodide uptake, H2O2 generation, thyroglobulin synthesis, and peroxidase enzyme level obviously are the main regulations. Many of these actions are thought to involve mediation of adenyl cyclase and subsequent activation of intracellular phosphokinases. Antithyroid drugs of the thiocarbamide group are competitive inhibitors of iodination under some circumstances, but if much iodide is present, they react with the oxidized iodine intermediate and are irreversibly inactivated themselves. Clinical problems involving defective peroxidase function are among the most frequent hereditary defects of thyroid hormone formation. Recognized abnormalities include deficient peroxidase, abnormality in binding of the peroxidase apoprotein to its prosthetic group, and other less well-identified abnormalities in peroxidase structure and function. Peroxidase is typically elevated in thyroid tissue from patients with hyperthyroidism sometimes deficient in cold thyroid nodules, and frequently diminished in tissue from patients with Hashimoto's thyroiditis.
 ...
PMID:Biosynthesis of thyroid hormone: basic and clinical aspects. 6 47

Rats, pretreated with thyroxine for 2 days, were given one or two iv injections of 500 mU of TSH; in some groups the second TSH dose was replaced by 0.75 micronmol isoproternol. The effects of the thyroid stimulators on the following parameters were studied: the number of exocytotic vesicles in the follicle cells; the incorporation of 125I into thyroid proteins, measured over periods of 5 min; and the thyroidal cAMP contents. At 2 h after TSH administration, a second dose of TSH failed to stimulate iodination while at 8 h the iodination response was "normal". Two hours after TSH the follicle cells contained practically no exocytotic vesicles but at 8 h they had a full supply of vesicles, and this was emptied by the second TSH injection. THE CAMP content was less increased by the second TSH injection than by the first one, but the stimulatory effect of the second TSH dose on cAMP was the same at 2 h and at 8 h; this indicates that the lack of iodination response at 2 h was not simply due to blocking of TSH receptors. Isoproternol, which acts on other receptors than does TSH, cause a similar cAMP increase incontrols and at 2 h and 8 h after TSH, but stimulated iodination only in controls and at 8 h after TSH; this supported the conclusion that the lack of iodination response to a second TSH dose at 2 h was not due to impairment of the adenylate cyclase-cAMP system. These observations taken together strongly indicate that a rapid iodination response to TSH depends on stimulated exocytosis which, in turn, requires a pool of exocytotic vesicles in the follicle cells. Such a coupling between exocytosis and iodination seems appropriate since by exocytosis uniodinated thyroglobulin and membrane, showing peroxidase activity histochemically, are delivered to the site of iodination, the apical cell surface.
 ...
PMID:Effects of thyrotropin on thyroglobulin exocytosis and iodination in the rat thyroid gland. 21 93

An electron microscopic histochemical technique for the concurrent localization of adenylate cyclase and endogenous peroxidase is described. The procedure involves incubation of glutaraldehyde fixed tissue in adenylate cyclase medium followed by washing and incubation in 3,3'-diaminobenzidine tetrahydrochloride medium to demonstrate peroxidase activity. Adenylate cyclase was localized at the cell surface of the tissue investigated (20 day fetal rat submandibular gland) while peroxidase was localized in the rough endoplasmic reticulum and secretory granules of some cells. Biochemical and histochemical controls indicate that the procedure is valid. The potential use of this procedure and variations of the procedure are discussed.
 ...
PMID:Concurrent cytochemical localization of adenylate cyclase and peroxidase in the developing rat submandibular gland. 91 43

The occurrence of serotonin in the human adrenal gland was demonstrated both by immuno-histochemical and biochemical approaches. Using specific polyclonal antibodies to serotonin, the presence of numerous immunoreactive cells was revealed by means of the peroxidase-antiperoxidase technique. These cells exhibited the morphological characteristics of mast cells. Combination of high performance liquid chromatography and electrochemical detection showed the presence of substantial amounts of both serotonin and its metabolite 5-hydroxyindolacetic acid in adrenocortical extracts. The role of serotonin in the regulation of steroidogenesis from human adrenocortical slices was studied in vitro using a perifusion system technique coupled to a specific radioimmunoassay for cortisol. Graded doses of serotonin (from 10(-8) M to 3 x 10(-7) M) increased cortisol production in a dose-dependent manner. Prolonged exposure of adrenal fragments to serotonin (10(-7) M) induced a biphasic response, i.e. a rapid and transient increase in cortisol secretion followed by a plateau phase, suggesting the existence of a desensitization phenomenon. The stimulatory effect of serotonin (10(-7) M) was not altered during infusion of the serotonin1 and/or serotonin2 receptor antagonists methysergide (10(-6) M) and ketanserin (10(-6) M), respectively. In contrast, ICS 205 930 (10(-6) M), a non-selective serotonin3/serotonin4 antagonist, totally abolished the response of adrenal slices to serotonin (10(-7) M). The benzamide derivative zacopride, considered as a serotonin4 agonist, induced a robust stimulation of cortisol secretion. In addition, the corticotropic effects of serotonin (10(-7) M) and zacopride (10(-6) M) were not additive. Incubation of adrenocortical fragments with zacopride (10(-6) M) or serotonin (10(-6) M) caused a significant increase in cAMP formation. Taken together, these data suggest that serotonin, locally released by intra-adrenal mast-like cells, may act as a paracrine factor to stimulate cortisol secretion in man. Our results also indicate that serotonin-induced corticosteroid production is mediated through activation of a serotonin4 receptor subtype positively coupled to adenylate cyclase.
 ...
PMID:Serotonin-induced stimulation of cortisol secretion from human adrenocortical tissue is mediated through activation of a serotonin4 receptor subtype. 137 44

Vasoactive intestinal peptide (VIP) and d-ala2-methionine enkephalinamide (DALA, a long-lasting enkephalin analogue) were used to investigate the peptidergic control of lacrimal gland function. To characterize the mechanism by which VIP stimulates and DALA inhibits lacrimal peroxidase secretion, the effect of these peptides on adenylate cyclase was measured. In addition, enzyme activity was measured in the presence of forskolin alone or in combination with DALA. VIP stimulated adenylate cyclase in a time- and dose-dependent manner. Negative control of adenylate cyclase was shown with the addition of DALA to membrane preparations. The enkephalin analogue inhibited basal activity approximately 65% at the maximum dose tested. The percent inhibition of VIP-stimulated activity by DALA was similar to the inhibition of basal activity. To determine if the inhibition of stimulated activity occurred at level of the VIP receptor, the effect of DALA on the response to forskolin was measured. Forskolin-stimulated adenylate cyclase activity was significantly reduced to approximately 50% in the presence of DALA. We conclude that lacrimal gland adenylate cyclase is subject to peptidergic regulation involving both stimulatory and inhibitory receptor-mediated controls.
 ...
PMID:Peptidergic stimulation and inhibition of lacrimal gland adenylate cyclase. 217 Feb 90

A unilateral injection of 6-OHDA (6 microgram/1.5 microliter) was made into the fields of Forel in order to estimate the effects of the destruction of ascending dopaminergic (DA) pathways on the denervation supersensitivity of DA D1 receptors in the rat striatum. DA-sensitive adenylate cyclase activity was markedly enhanced in the anteromedian part of the striatum 3 weeks after the lesion (+68%) and remained elevated for several weeks thereafter (+36%). A different response occurred in the laterodorsal striatum, where the increase in DA-sensitive adenylate cyclase activity was less pronounced after 3 weeks (+40%) and no longer present after 7 weeks. Estimations of catecholamine levels indicated that the lesion made destroyed not only nigrostriatal DA neurons but other ascending catecholaminergic fibers projecting into the cerebral cortex as well. In addition, retrograde transport experiments made with wheat germ agglutinin coupled to horseradish peroxidase indicated that the anteromedian part of the striatum, but not the laterodorsal one, receives both an ipsi- and contralateral cortical projection originating in the prefrontocortical DA field. When the destruction by 6-OHDA of this contralateral DA innervation was combined to the unilateral lesion of the fields of Forel, the increase in DA-sensitive adenylate cyclase activity in each striatal area 3 or 7 weeks postlesion was prevented. This effect was due to DA denervation of the prefrontal cortex since striatal D1 denervation supersensitivity was still observed when contralateral ascending noradrenergic fibers were selectively destroyed by a 6-OHDA lesion made laterally to the pedunculus cerebellaris superior. These results suggest that, by controlling the activity of corticostriatal neurons, the mesocorticoprefrontal DA neurons exert a permissive role on the development of D1-receptor denervation supersensitivity in specific areas of the striatum.
 ...
PMID:Nondopaminergic prefrontocortical efferent fibers modulate D1 receptor denervation supersensitivity in specific regions of the rat striatum. 247 23

Addition of a cholinergic agonist carbachol and vasoactive intestinal peptide (VIP) to dispersed rat exorbital lacrimal gland acini produces protein secretion, measured by secretion of the enzyme peroxidase, that was statistically significantly greater than additive (potentiated). To determine where in stimulus-secretion coupling these secretagogues interact to potentiate secretion, rat exorbital gland acini were incubated simultaneously with cyclic AMP- and Ca2+-dependent agonists and protein secretion, cyclic AMP level, or Ca2+ concentration measured. As a measure of protein secretion, the supernatant obtained after centrifugation of acini was analyzed for peroxidase, a protein secreted by rat lacrimal glands. Interaction did not occur at the receptor level, because peroxidase secretion also was potentiated by simultaneous addition of carbachol and forskolin, which activates the catalytic subunit of adenyl cyclase. A potentiated increase in the cyclic AMP level did not potentiate protein secretion, because the level was the same with VIP as with carbachol and VIP added together at concentrations that potentiated peroxidase secretion. A potentiated increase in free intracellular [Ca2+] did not potentiate protein secretion, because [Ca2+] was greater with carbachol than with carbachol and VIP added together at concentrations that potentiated peroxidase secretion. We conclude that cholinergic- and VIP-dependent pathways interact to potentiate lacrimal gland protein secretion after the rise of intracellular cyclic AMP or Ca2+.
 ...
PMID:Role of cyclic AMP and Ca2+ in potentiation of rat lacrimal gland protein secretion. 284 62

In defined conditions, glutaraldehyde was shown to tightly bind cell membranes to flexible microtiter plates without significant alteration of the antigenic and functional properties of membrane proteins. In the presence of 0.06% glutaraldehyde, human thyroid membranes were bound to plastic firmly enough to resist numerous washing and flicking steps; the coated membranes remained almost unaltered with regard to monoclonal antibody and thyrotropin binding as well as adenylate cyclase and peroxidase activities. Based on the use of thyroid membrane-coated microtiter plates, a versatile solid-phase assay was developed which allowed screening of anti-membrane monoclonal antibodies, detection of thyrotropin-displacing activity in hormone and antibody preparations, and monitoring of fractionation experiments of solubilized membrane antigens and thyrotropin receptor. It was concluded that the use of glutaraldehyde for coating cell membranes to flexible microtiter plates enabled the establishment of simple, rapid, and reliable assays for detection and quantitation of membrane proteins and molecules interacting with membranes.
 ...
PMID:Cell membrane coating with glutaraldehyde: application to a versatile solid-phase assay for thyroid membrane proteins and molecules interacting with thyroid membranes. 299 21

Forskolin is a unique diterpene activator of adenylate cyclase which has been extensively used in the study of cAMP generating systems. This report describes the production of antibodies to forskolin and the optimization of two sensitive assay methods for such antibodies. 7-0-Hemisuccinyl 7-deacetyl forskolin, coupled to either human serum albumin or goat IgG, was injected into goats to elicit antibodies to the forskolin hapten. Two assay methods, a radioimmunoassay with [12-3H]forskolin as a tracer and a colorimetric enzyme-linked immunosorbent assay (ELISA) with horse radish peroxidase-labelled rabbit anti-goat IgG as an indicator, were optimized to test for the presence of forskolin antibodies in antisera and isolated IgG fractions. The titers for forskolin antisera were 4000-10000. Both assay methods can be adapted to quantify forskolin and its protein conjugates. The availability of antibodies to this diterpene will be useful in accelerating the understanding of the mechanism of adenylate cyclase activation by forskolin.
 ...
PMID:Production and assay of antibodies to an activator of adenylate cyclase, forskolin. 369 25

Stimulation of endocytosis is a very early effect of thyrotropin on thyroid. However, the relationship of the endocytotic process to the many other thyrotropin effects on thyroid is not clearly defined. Since phagocytosis in isolated thyroid cells is a presumed model for in vivo endocytosis of colloid, we induced phagocytosis in isolated thyroid cells by incubating them at 37 degrees C with 0.109-mu diameter polystyrene microbeads; phagocytosis was confirmed in each experiment by electron microscopy and/or spectrophotometric analysis of dioxane cell extracts. Cells incubated with 50-100-mu diameter polystyrene macrobeads (too large to ingest) served as controls. Microbead-induced phagocytosis in isolated thyroid cells was consistently accompanied by increases in: (a) cyclic 3',5'-adenosine monophosphate-(14)C formation from adenine-8-(14)C (66%); (b) iodide-(131)I trapping (40%); (c) protein and RNA synthesis (30%); (d) phospholipogenesis (50%); (e) alpha-aminoisobutyric acid-1-(14)C uptake (15%). 50- to 100-mu diameter polystyrene macrobeads did not influence cell function in any of these experiments. Aminotriazole, 5 x 10(-3) (M), a peroxidase inhibitor, blocked the stimulatory effect of microbead-induced phagocytosis on phospholipogenesis only. These studies indicate that in isolated thyroid cells the phagocytotic process, per se, may alter activity of the membrane-bound adenyl cyclase enzyme. The resultant increase in cyclic 3',5'-adenosine monophosphate may be a triggering mechanism for (some) subsequent metabolic changes occuring during phagocytosis. Since these changes mimic those induced by thyrotropin, it is suggested that a variety of thyrotropin effects on thyroid may be secondary to stimulation of colloid resorption and hormone secretion.
 ...
PMID:Stimulatory effects of induced phagocytosis on the function of isolated thyroid cells. 434 55


1 2 3 Next >>