Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-nucleated red blood cells from rats contain adenyl cyclase, the activity of which is predominantly localized in the reticulocytes. Basal enzyme activities in membrane preparations from reticulocyte-rich blood (pretreatment of rats with acetyl-phenylhydrazide: about 60% reticuloytes) are about 5 times higher than in preparations from reticulocyte-poor blood (untreated animals: 2-3% reticulocytes). The enzyme activities are stimulated 10-fold by sodium fluoride (10(-2)M) and 6 to 8-fold by isoprenaline (10(-4)M). Adenyl cyclase activities in membrane preparations from reticulocyte-rich and reticulocyte-poor blood can be ascribed to identical enzymes since identical apparent Km (ATP; 3 times 10(-4)M, Ka (isoprenaline; 3 times 10(-6)M) and Ki (propranolol vs. isoprenaline; 3 times 10(-7)M) values were obtained in both preparations. Besides NaF, only phenylethanolamine derivatives with beta-adrenergic receptor stimulant properties were effective as stimulators of adenyl cyclase activity. The affinities (apparent Ka values) of the investigated compounds decreased in the order isoprenaline--hexoprenaline--fenoterol--salbutamol--adrenaline--terbutalin--noradrenaline--phenylephrine. For maximal intrinsic activity, the catechol structure was essential; the relative intrinsic activities of resorcinol derivatives did not exceed 0.6. The isoprenaline-stimulated adenyl cyclase activities in erythrocyte membrane preparations were competitively inhibited by beta-adrenergic blocking drugs, the affinities (apparent Ki values) decreasing in the order prindolol--penbutolol--propranolol--practolol. The dextrorotatory enantiomers of penbutolol and propranolol were 1/100 to 1/200 as active as the resp. levorotatory enantiomers. From experiments with alpha-adrenergic agonists (e.g. phenylephrine) and antagonists (e.g. phentolamine), it is concluded that alpha-adrenergic receptors do not interfere with the beta-adrenergically-mediated cAMP formation in these particular membranes. A variety of hormones and drugs known to stimulate denyl cyclase activities in various tissues, e. g. ACTH, glucagon, STH, erythropoietin, prostaglandin E1 etc. did not affect adenyl cyclase activity in reticulocyte-rich erythrocyte membrane preparations. In contrast to adenyl cyclase activity, phosphodiesterase activities in erythrocyte membrane and cytoplasmic fractions were only twice as high in reticulocyte-rich as in reticulocyte-poor preparations. From the experiments described, it is obvious that the adenyl cyclase of the rat reticulocyte is subject to monovalent-hormonal, i.e. beta-sympathomimetic stimulation. Moreover, the premature red blood cell provides a useful model for quantitative studies of the interaction of drugs with the beta-adrenergic receptor.
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PMID:The beta-adrenergic receptor-adenyl-cyclase system of rat reticulocytes: effects of adrenergic stimulants and inhibitors. 24 Jan 35

Adenyl cyclase (AC) has been studied in homogenates and crude plasma membranes from normal and denervated red and white skeletal muscle from male rats. Basal-, NaF- and epinephrine-stimulated activities were increased in homogenates of both types of muscles after nerve transection, supporting a possible role of the cAMP-AC system in the neurotrophic control of skeletal muscle. AC-specific activity was increased 10 times in crude plasmic membranes from normal muscle if compared to that of homogenate. It was decreased in crude plasmic membrane from denervated muscle. The correlation of our results with other results on cAMP concentrations and cAMP phosphodiesterase (PDE) activities in denervated muscle suggests that factors other than AC and PDE might control the synthesis and degradation of cAMP.
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PMID:Adenyl cyclase in normal and denervated skeletal muscles. 62 74

The effect of light on adenyl cyclase (E.C. 4.6.1.1) and 3':5'-cyclic-AMP-phosphodiesterase (E.C. 3.1.4.17) activity of Trichoderma viride was investigated. Adenyl cyclase proved to be a membrane-associated enzyme, requiring Mn2+ and was activated by light. In contrast, 3':5'-cyclic-AMP-phosphodiesterase showed no light-stimulated activity. The activity of 3':5'-cyclic-AMP-phosphodiesterase was present mainly in the cytosol and was stimulated by Mg2+.
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PMID:Light-activated adenyl cyclase from Trichoderma viride. 137 60

The activities of cyclic AMP phosphodiesterase (3',5'-cyclic nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) and adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and calmodulin content during development of chick ventricular myocardium were determined. The specific activity of cyclic AMP phosphodiesterase was relatively low in early embryos, increased during embryogenesis by about 4-fold to reach highest values just before hatching, and then decreased by approx. 30% within 1 week after hatching. In contrast, adenylate cyclase did not change during embryonic development, but increased by approx. 50% within 1 week after hatching. Calmodulin content remained constant at 9 micrograms/g wet wt. during embryonic development and decreased to 6 micrograms/g wet wt. by 1 week after hatching. DEAE-Sephacel chromatography of chick ventricular supernatant revealed a single major form of cyclic nucleotide phosphodiesterase activity in early embryonic (9-day E) and hatched (6-day H) chicks. This enzyme form was eluted at approx. 0.27 M-sodium acetate, hydrolysed both cyclic AMP and cyclic GMP, and was sensitive to stimulation by Ca2+-calmodulin, with an apparent Km for calmodulin of approx. 1 nM. In contrast, ventricular supernatant from late-embryonic (18-day E) chicks contained two forms of phosphodiesterase separable on DEAE-Sephacel: the same form as that seen at other ages, plus a cyclic AMP-specific form which was eluted at approx. 0.65 M-sodium acetate and was insensitive to stimulation by Ca2+-calmodulin. The ontogenetic changes in cyclic AMP phosphodiesterase activity in chick ventricular myocardium are consistent with reported ontogenetic changes in the steady-state contents of cyclic AMP in this tissue and suggest that this enzyme may be responsible for the changes that occur in this nucleotide during development of chick myocardium.
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PMID:Ontogenetic changes in adenylate cyclase, cyclic AMP phosphodiesterase and calmodulin in chick ventricular myocardium. 282 Mar 84

In the aortas and mesenteric arteries from spontaneous hypertensive rats and in the aortas from stress- and desoxycorticosterone-acetate-hypertensive rats, the intracellular cGMP: cAMP ratios were significantly elevated when compared to the ratios in the aortas of the respective controls. Decreases in the intracellular cAMP or cGMP levels were consistently associated with increased activity of the cyclic-nucleotide-specific low K(m) phosphodiesterase (3':5'-cAMP 5' nucleotidohydrolase, EC 3.1.4.17). Increases in intracellular cGMP levels were associated with elevated guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activity. Furthermore, adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity was less sensitive to stimulation by the beta-adrenergic stimulant isoproterenol in both the aortas and the hearts of the hypertensive animals. These changes could provide the biochemical basis for the (a) increased vascular smooth muscle tone and peripheral resistance observed in these animals, (b) increased reactivity to norepinephrine, and (c) decreased ability of aortas from hypertensive rats to relax. The presence of these same effects in different etiologic types of hypertension indicates that this aberration in cyclic nucleotide metabolism may represent a common metabolic defect basic to the hypertensive syndrome irrespective of etiology.
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PMID:Aberrations of cyclic nucleotide metabolism in the hearts and vessels of hypertensive rats. 415 74

The monokaryotic mycelia of a mutant strain, fis(c), of Coprinus macrorhizus, which are able to form monokaryotic fruiting bodies in the light, failed to form any fruiting bodies in darkness. A dikaryon and a mutant strain, ds, formed malformed fruiting bodies in darkness. Illumination for 1 day of fis(c) mycelia grown in darkness for 4 days or longer was effective in inducing malformed fruiting bodies. The accumulation of adenosine 3':5'-cyclic monophosphate in the illuminated mycelia of strain fis(c) was demonstrated. The illuminated mycelia of strain fis(c) produced high levels of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and phosphodiesterase (3':5'-cyclic-AMP 5'-nucleotidohydrolase, EC 3.1.4.17), which degrades cAMP, while the dark-grown mycelia showed no or very low activities of these enzymes. Dikaryotic mycelia and monokaryotic mycelia of strain ds produced significant amounts of these enzymes even in darkness. When the dark-grown mycelia of strain fis(c) were exposed to continuous light, the activities of adenylate cyclase and phosphodiesterase increased rapidly after a lag period whose length depends on the culture age of mycelia. Cycloheximide inhibited the increase in these enzyme activities stimulated by light. When the fis(c) mycelia were exposed to continuous light, an increase in cAMP-binding activity was observed. A possible participation of cAMP in the formation of fruiting bodies in C. macrorhizus is discussed.
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PMID:The effect of light on fruiting body formation and adenosine 3':5'-cyclic monophosphate metabolism in Coprinus macrorhizus. 436 Sep 45

The intestinal transport of 5-methyltetrahydrofolate and pteroylmonoglutamate was examined in everted sacs of rat jejunum exposed to compounds which increase intracellular cyclic adenosine-3', 5'-monophosphate. Adenyl cyclase stimulators (hydrocortisone and prostaglandin), phosphodiesterase inhibitors (3-isobutyl-l-methylxanthine, aminophylline and papaverine), and dibutyryl adenosine-3',5'-cyclicmonophosphate added to the mucosal medium inhibit the mucosal-to-serosal transport of physiological concentrations of 5-methyltetrahydrofalate and pteroylmonoglutamate. Transport inhibition is correlated with the ability of these agents to increase cellular cyclic adenosine-3', 5'-monophosphate. The active, carrier-mediated transport system of folate compounds is highly sensitive to the increase in cyclic adenosine-3', 5'-monophosphate level, while the diffusion system is insensitive. These data indicate that the active transport system of folates is modulated by cellular cyclic adenosine-3', 5'-monophosphate.
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PMID:Cyclic adenosine-3',5'-monophosphate and folate transport in rat jejunum. 619 95

Previous studies have noted profound similarities between the regulation of light-activated 3',5'-cyclic nucleotide phosphodiesterase (3',5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) in retinal rods and hormone-activated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] in a variety of tissues. We report here the functional exchange of components isolated from the photoreceptor system, which displayed predicted functional characteristics when incubated with recipient adenylate cyclase systems from rat cerebral cortical and hypothalamic synaptic membranes and frog erythrocyte ghosts. We demonstrate functional exchange of photoreceptor components at each of three loci: the hormone receptor, the GTP-binding protein (GBP), and the catalytic moiety of adenylate cyclase. Illuminated (but not unilluminated) rhodopsin was fund to mimic the hormone-receptor complex, causing GTP-dependent activation of adenylate cyclase. The photoreceptor GBP complexed with guanosine 5'-[beta, gamma)imidotriphosphate (p[NH]ppG) produced a marked activation of recipient adenylate cyclase systems. Much smaller activation was observed when GBP was not complexed with p[NH]ppG. A heat-stable photoreceptor phosphodiesterase inhibitor reduced both basal and Mn2+-activated adenylate cyclase activities and this inhibition was reversed by photoreceptor GBP.p[NH]ppG. These data demonstrate a remarkable functional compatibility between subunits of both systems and furthermore imply that specialized peptide domains responsible for protein-protein interactions are highly conserved.
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PMID:Functional exchange of components between light-activated photoreceptor phosphodiesterase and hormone-activated adenylate cyclase systems. 628 49

Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and adenyl cyclase and phosphodiesterase activities were determined in the specialized myocardial tissue of the conduction system of bovine heart and then compared with those in the ordinary myocardial tissue. The conduction system was comprised of the atrioventricular node (A-V node), the His bundle and the right and the left bundle branches (RBB and LBB). The content of cyclic AMP was higher in the ordinary myocardial tissue than in the specialized myocardial tissue. In the specialized myocardial tissue, its content was highest in the A-V node and lower in the His bundle than in the LBB and the difference between the contents in the RBB and the LBB was not significant. Adenyl cyclase activity as well as the content of cyclic AMP was higher in the ordinary myocardial tissue than in the specialized myocardial tissue. Its activity was higher in the A-V node than in the His bundle or the RBB, and the activities in the His bundle, the RBB and the LBB were similar. Phosphodiesterase activity was higher in the ordinary myocardial tissue than in the A-V node, and the activities in these 4 sections of the conduction system were similar.
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PMID:Cyclic adenosine 3', 5'-monophosphate, adenyl cyclase and phosphodiesterase in the conduction system of bovine heart. 630 Apr 81


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