Showing papers on "Cyclase published in 1970"
TL;DR: This study demonstrates directly the binding of ACTH to its biologically significant site in direct proportion to their biological activity.
Abstract: Pure monoiodo ACTH-(125)I was prepared that was biologically active and free of unlabeled ACTH. Extracts of adrenal cortex that contained ACTH-sensitive adenyl cyclase, bound ACTH-(125)I; extracts that lacked the ACTH-sensitive cyclase did not bind ACTH-(125)I. Unlabeled ACTH inhibited the binding of ACTH-(125)I. Five ACTH derivatives which varied widely in biological activity were tested. All inhibited the binding of ACTH-(125)I in direct proportion to their biological activity. Albumin, insulin, and four unrelated iodinated hormones were inert. The addition of excess hormone or acetic acid produced rapid dissociation of bound ACTH-(125)I. This study demonstrates directly the binding of ACTH to its biologically significant site.
280 citations
TL;DR: An electron microscopic procedure has been developed, using rat liver, for the localization of hormone-sensitive adenyl cyclase, which finds that Isoproterenol-sensitiveAdenyl Cyclase is located almost exclusively in the parenchymal cells, while glucagon-sensitive AdenylCyclases is located primarily in the reticulo-endothelial cells but is also present in parenchymal cells.
Abstract: An electron microscopic procedure has been developed, using rat liver, for the localization of hormone-sensitive adenyl cyclase. Isoproterenol-sensitive adenyl cyclase is located almost exclusively in the parenchymal cells. In contrast, glucagon-sensitive adenyl cyclase is located primarily in the reticulo-endothelial cells but is also present in parenchymal cells. Sodium fluoride-sensitive adenyl cyclase is found in both cell types.
168 citations
TL;DR: The demonstrated inhibition of colloid droplet formation and absence of an effect on thyroidal adenyl cyclase or cyclic 3':5'-phosphodiesterase suggests a colchicine-sensitive role for microtubules in colloid endocytosis in the thyroid gland.
Abstract: Colchicine and other microtubule-active agents have been found to block the release, stimulated by either thyroid-stimulating hormone or by dibutyryl cyclic adenosine 3':5'-monophosphate, of (131)I from previously (131)I-labeled mouse thyroid glands in vitro. The time and concentration characteristics of these inhibitors are consistent with their actions on microtubules in other systems. [(3)H]colchicine was also shown to be bound to a soluble 6S protein of bovine thyroid slices similar to the protein identified in other systems as a microtubular subunit. The demonstrated inhibition of colloid droplet formation and absence of an effect on thyroidal adenyl cyclase or cyclic 3':5'-phosphodiesterase suggests a colchicine-sensitive role for microtubules in colloid endocytosis in the thyroid gland.
151 citations
TL;DR: Calcium is thought to be required for the binding of adrenal corticotrophic hormone (ACTH) to its cellular receptor and inhibit the activation of adenyl cyclase by ACTH in subcellular particles from adipose and adrenal tissue.
Abstract: CALCIUM is thought to be required for the binding of adrenal corticotrophic hormone (ACTH) to its cellular receptor1–5: in its absence, ACTH fails to stimulate steroidogenesis in the adrenal or lipolysis in adipose tissue1,2,6,7. The actions of other lipolytic hormones such as adrenaline and glucagon do not require calcium1–3. On the other hand, high calcium concentrations (>1 mM) inhibit the activation of adenyl cyclase by ACTH in subcellular particles from adipose and adrenal tissue8,9. The sites of these effects of calcium have not been unequivocally located.
149 citations
TL;DR: The effects of cyclic AMP and its dibutyryl derivative on the contractile performance of isolated cat right ventricular papillary muscles are examined, consistent with the hypothesis that the positive inotropic effects of catecholamines are mediated by cyclicAMP.
Abstract: The positive inotropic effects of catecholamines have been postulated to result from an increase in the intracellular level of cyclic AMP (adenosine 3',5'-monophosphate) produced by activation of adenyl cyclase. Although lack of an inotropic effect by exogenously administered cyclic AMP has cast doubt on this hypothesis, cardiac cells are not readily permeable to cyclic AMP. The N6-2'-O-dibutyryl derivative of cyclic AMP is thought to enter cells more readily and is resistant to enzymatic degradation by phosphodiesterase. We examined the effects of cyclic AMP and its dibutyryl derivative on the contractile performance of isolated cat right ventricular papillary muscles. Cyclic AMP (1 x 10-4 to 5 x 10-3M) had no effect on papillary muscle function. However, dibutyryl cyclic AMP caused a concentration-dependent increase in isometric tension and rate of tension development, the threshold concentration being 5 x 10-4M. The increments in tension (4.5 ± 0.4 g/mm2) and rate of tension development (58.4 ± 5.4 g/m...
136 citations
TL;DR: It is suggested that adenyl cyclase in higher animals is controlled by specific proteins which are coupled with the enzyme and inhibit its activity, and Fluoride appears to counteract the inhibition by a process which is not readily reversible.
132 citations
TL;DR: The detergent, Lubrol-PX, solubilized approximately 90–100% of the particulate adenyl cyclase in cat left ventricular homogenates and revealed a virtual absence of particulate material in the ultracentrifuge supernatants.
127 citations
TL;DR: The results suggest that Li inhibits vasopressin-induced antidiuresis at the level of adenyl cyclase, suggesting that NaCl may modulate the kidney response to vasoppressin.
126 citations
TL;DR: The results show that the hormone receptor proteins are separate from the adenyl cyclase, a finding which indicates at least two types of membrane bound epinephrine.
126 citations
TL;DR: The effect of parathyroid hormone was much greater with tubules isolated from the renal cortex than with those from the medulla, and incorporating an ATP-regenerating system (phosphoenolpyruvates and pyruvate kinase) enhanced the sensitivity of the system.
Abstract: Tubules were isolated from kidneys of rats after incubation with collagenase and the effect of parathyroid hormone on adenyl cyclase in this tissue was studied. Adenyl cyclase in homogenates of tubules was assayed by measuring conversion of ATP-α-32P to cyclic 3′,5′-AM32P. Incorporating an ATP-regenerating system (phosphoenolpyruvate and pyruvate kinase) enhanced the sensitivity of the system. Virtually all of the enzyme activity in the renal cortex was found in the tubules. Parathyroid hormone caused rapid activation of the enzyme in tubules from the renal cortex; enzyme activity was directly proportional to the concentration of parathyroid hormone over the range of 0.05 to 5 μg/ml. The effect of parathyroid hormone was much greater with tubules isolated from the renal cortex than with those from the medulla. In contrast, arginine vasopressin activated the enzyme in the medulla but not the cortex. Epinephrine, glucagon and thyrocalcitonin caused an increase in enzyme activity but showed no dose-response ...
121 citations
TL;DR: The adenyl cyclases of chick oviduct and rat prostate were not stimulated by estrogen and testosterone, respectively, suggesting that growth and differentiation of these target tissues are not mediated by adenosine 3',5'-monophosphate.
Abstract: The adenyl cyclases of chick oviduct and rat prostate were not stimulated by estrogen and testosterone, respectively, suggesting that growth and differentiation of these target tissues are not mediated by adenosine 3',5'-monophosphate. Estrogen acutely activated adenyl cyclase in the castrate rat uterus, but this was prevented by administration of DL-propranolol, suggesting that the effect was mediated by catecholamines. Progesterone produced a delayed stimulation of oviduct adenyl cyclase preceding and concomitant with the induction of synthesis of avidin.
TL;DR: The level of endogenous cyclic AMP in the rat brain in vivo began to increase markedly between the third and sixth days after birth, as did the ability of norepinephrine to stimulate the formation of cyclicAMP in brain tissue in vitro.
Abstract: The level of endogenous cyclic AMP in the rat brain in vivo began to increase markedly between the third and sixth days after birth, as did the ability of norepinephrine to stimulate the formation of cyclic AMP in brain tissue in vitro. Adenyl cyclase activity in broken cell preparations, when measure in the absence of sodium fluoride, increased with age up to a point, but began to decline between the fifth and ninth days postpartum. Activity continued to increase when measured in the presence of fluoride, suggesting that the apparent stimulatory effect of this ion may in fact be the reversal of an inhibitory influence which is absent or almost absent at birth. Cyclase activity at all ages was restricted to particulate matter, whereas apparent phosphodiesterase activity was present in particulate as well as soluble fractions. The catabolic system for cyclic AMP developed in a similar manner in both fractions. Theophylline produced the same degree of inhibition of this system at all ages.
TL;DR: A rapid and convenient chemical assay for the enzyme d-glucose 6-phosphate-1l-myoinositol 1-ph phosphate cyclase is described and the K(m) of the enzyme, 7.5+/-2.5x10(-4)m), was identical with that measured by the radiochemical method.
Abstract: A rapid and convenient chemical assay for the enzyme d-glucose 6-phosphate-1l-myoinositol 1-phosphate cyclase is described. The 1l-myoinositol 1-phosphate formed enzymically was oxidized with periodic acid liberating inorganic phosphate, which was assayed. myoInositol 2-phosphate can be assayed in the same way. Glucose 6-phosphate and other primary phosphate esters gave only very small quantities of inorganic phosphate under the conditions described. The K(m) of the enzyme for d-glucose 6-phosphate, 7.5+/-2.5x10(-4)m, was identical with that measured by the radiochemical method. 2-Deoxy-d-glucose 6-phosphate was a powerful competitive inhibitor, K(i) 2.0+/-0.5x10(-5)m, but was not a substrate for the enzyme.
TL;DR: Data are presented which indicate that the activities of the glucagon and epinephrine responsive components of hepatic adenyl cyclase vary separately as a function of age, sex and steroid hormone levels in the rat.
Abstract: This study presents data which indicate that the activities of the glucagon and epinephrine responsive components of hepatic adenyl cyclase vary separately as a function of age, sex and steroid hormone levels in the rat. These observations lend support to the hypothesis that the 2 hormonally sensitive adenyl cyclase systems in liver are independent. (Endocrinology 86: 154, 1970)
TL;DR: Data indicate that the increase in endogenous cyclic AMP brought about by luteinizing hormone is due to a stimulation of the adenyl cyclase rather than to an inhibition of the phosphodiesterase.
01 Jan 1970
TL;DR: In this article, Chen et al. described a rapid and convenient chemical assay for the enzyme D-glucose 6-phosphate-lL-myoinositol 1-phophosphate cyclase, which can be used to assay other inositol monophosphates.
Abstract: A rapidandconvenient chemical assay fortheenzyme D-glucose 6-phosphateIL-myoinositol 1-phosphate cyclase isdescribed. TheIL-myoinositol 1-phosphate formedenzymically was oxidized withperiodic acidliberating inorganic phosphate, whichwas assayed. myolnositol 2-phosphate can beassayed inthesame way. Glucose 6-phosphate andotherprimaryphosphate esters gave onlyvery small quantities ofinorganic phosphate undertheconditions described. TheKm ofthe enzyme forD-glucose 6-phosphate, 7.5 + 2.5x 10-4M, was identical withthat measuredbytheradiochemical method.2-Deoxy-D-glucose 6-phosphate was a powerful competitive inhibitor, KL2.0 ± 0.5x 10-5 M, butwas notasubstrate forthe enzyme. The enzyme D-glucose 6-phosphate-lL-myoinositol 1-phosphate cyclase hasbeenpartially purified fromyeast(Chen & Charalampous, 1966; Charalampous & Chen,1966), Neurospora (Pina& Tatum,1967), higher plants (VonRuis, Molinari & Hoffinann-Ostenhof, 1967)and animaltissues (Eisenberg, 1967)andsome aspects ofitsmechanismofaction havebeeninvestigated (Barnett & Corina, 1968;Sherman, Stewart& Zinbo,1969). However, further purification andinvestigation of thekinetic properties oftheenzyme havebeen severely hamperedbythelength anddifficulty of theradiochemical assayfortheenzyme, inwhich radioactive D-glucose 6-phosphate isenzymically converted into1L-myoinositol 1-phosphate, which mustthenbeconverted intoinositol andseparated fromcontaminating glucose beforecounting of radioactivity, preferably as the recrystallized hexa-acetate. An alternative assayhasbeenused(Eisenberg, 1967)inwhicha specific phosphatase, inactive towardsD-glucose 6-phosphate, isextracted from rattestes andusedtorelease inorganic phosphate enzymically fromtheIL-myoinositol 1-phosphate. Theinorganic phosphate isthenmeasured. Thispaper describes a rapid andsimple chemical assay fortheinositol phosphate produced bythe cyclase. Themethodcan beusedtoassayother inositol monophosphates.
TL;DR: Sr2+ was almost as effective as Ca2+ in reversing the inhibition by the chelating agent, while Mg2+ and Ba2+ were ineffective and higher concentrations of Ca2- inhibited the formation of the nucleotide.
TL;DR: The elevated levels of cyclic AMP seen in brain slices after incubation withadenosine are due to both stimulation of an adenyl cyclase and to conversion of adenosine to cyclicAMP.
TL;DR: Adenyl cyclase activity was assayed in a plasma membrane fraction prepared from bovine thyroid using sucrose gradients and found to contain higher specific activity DPNH-cytochrome C reductase than the original homogenate.
TL;DR: Since thymol causes a similar dissociation of hormone- and F(-)-stimulated adenyl cyclase, it is concluded that the surface properties of these agents best account for their effects on adenol cyclase.
Abstract: Chlorpromazine (3 × 10-4 M) prevents the stimulation of adenyl cyclase activity in thyroid membranes produced by thyrotropin and prostaglandin, ACTH stimulation of adenyl cyclase in adrenal tissue, and glucagon- and epinephrine-stimulation of adenyl cyclase activity in liver. Baseline activity is unaffected. Parathyroid hormone stimulation of kidney preparations was not inhibited under these conditions. At chlorpromazine concentrations >3 × 10-4 M F--stimulated cyclase activity of thyroid and adrenal tissue was increased. Other phenothiazines, trifluoperazine, and prochlorperazine, have similar effects on thyrotropin and F--stimulated cyclase activity of thyroid. Na+- K+-dependent ATPase of thyroid is also inhibited by chlorpromazine. Since thymol causes a similar dissociation of hormone- and F--stimulated adenyl cyclase, it is concluded that the surface properties of these agents best account for their effects on adenyl cyclase.
TL;DR: Thyroxine and triiodothyronine stimulated the conversion of ATP to 3′,5′-AMP (cAMP) by ejaculated rhesus monkey (Macaca mulatta) spermatozoa, with maximal stimulation occurring at a hormone level of 4 μM.
TL;DR: Alcohol produced a reversible activation of the glucagon responsive cyclase but did not activate the epinephrine responsive component, which further emphasizes the differences in the properties of the 2 hepatic cyclase systems.
Abstract: The effects of short chain alcohols (1 through 4 carbons) on hepatic cyclase were examined. Alcohol produced a reversible activation of the glucagon responsive cyclase but did not activate the epinephrine responsive component. The activation was accompanied by changes in the kinetic properties of the glucagon responsive cyclase and could not be explained in terms of enhanced Mg†† binding. These changes could reflect modifications of the solvent environment or binding of alcohol to a single site on the enzyme. The selective nature of this activation further emphasizes the differences in the properties of the 2 hepatic cyclase systems. (Endocrinology 87: 1075, 1970)
TL;DR: The data show that homogenates of human leukocytes, platelets and liver are capable of synthesizing cyclic AMP, and that such preparations are responsive to hormonal stimulation and further study may establish a relationship between adenyl cyclase stimulation and chemotaxis or phagocytic activity of circulatingLeukocytes.
TL;DR: A role of an adenyl cyclase system in the mechanism of steroid hormone action in insects is suggested, based on the fact that Mg 2+ is required for an optimal response of region 78B upon induction of its activity by ecdysterone.
TL;DR: The observation that different types of proteins are more rapidly phosphorylated in the presence of cAMP does indicate that this mechanism alone would allow the cyclic nucleotide to regulate many different aspects of cell function, from gene transcription to enzyme activity.
Abstract: A hormone is an effector molecule produced in low concentration by one cell which evokes a physiological response in another. In vertebrates, nu merous classes of chemically unrelated compounds such as polypeptides, amino acids, amines, fatty acid derivatives, and steroids have hormonal activity. Certain of these substances probably are themselves the primary intracellular effectors, whereas others clearly function at the cell surface, where they activate the membrane-bound enzyme, adenyl cyclase, and thereby stimulate the production of adenosine-3',S'-cyclic phosphate (cAMP) from ATP (1, 2). The intracellular effects of the cyclic nucleotide (the so called "second messenger") are responsible for the action of those hormones that stimulate its synthesis. Indirect experiments in fat cell preparations suggest that there is only a single species af adenyl cyclase that can be stim ulated by different hormones through interaction with hormone-specific membrane receptors (3, 4). However, this mechanism will not be truly un derstood until the cyclase is purified from hormonally responsive tissues, and its activation studied in further detail in vitro (5). The major question about the mechanism of action of these hormone!' has now become that of the intracellular action of cAMP itself. The majority of this review will not deal with this problem since it has been discussed extensively elsewhere (see 1, 2, 6 for example), but a brief survey might be useful before considering the other hormones that are less well understood. In multicellular organisms cAMP is a positive allosteric effector for the phosphorylation of various proteins by ATP. A cAMP-dependent kinase has been found in muscle (7), brain (8), and a number of other vertebrate and invertebrate tissues (8, 10). The macromolecular substrates for the kinase reactions are either enzymes (e.g. 7) or structural proteins such as the histones (11-13). Kuo & Greengard (9) have suggested that the only action of cAMP is to stimulate protein phosphorylation. Although this may be an oversimplification, the observation that different types of proteins are more rapidly phosphorylated in the presence of cAMP does indicate that this mechanism alone would allow the cyclic nucleotide to regulate many different aspects of cell function, from gene transcription to enzyme activity. Langan
TL;DR: Evidence that the augmentation of myocardial contractility produc... shows that the activity of many hormones can be related to their capacity to increase adenyl cyclase activity in their target organs.
Abstract: The activity of many hormones can be related to their capacity to increase adenyl cyclase activity in their target organs. Evidence that the augmentation of myocardial contractility produc...
TL;DR: Hypophysectomy failed to antagonize the stimulatory effect of ovariectomy and also failed to alter the inhibitory effects of estrogen treatment, indicating that estrogens do not act via release of gonadotropins.
Abstract: Adenyl cyclase activity of rat pineal gland homogenates was measured from the rate of conversion of ATP-14C to radiolabeled cyclic 3',5'-AMP. Norepinephrine stimulated adenyl cyclase activity of male rat pineal glands to a greater extent than that of female rat pineals. Orchiectomy or testosterone treatment of either male or female rats failed to alter pineal adenyl cyclase activity, but ovariectomy slightly increased the stimulatory effect of norepinephrine. Administering estradiol to ovariectomized rats for 2 days inhibited the norepinephrine- and sodium fluoride-induced activation of adenyl cyclase. No inhibition was observed when the steroid was given 1 hr before sacrifice or when estradiol was added in vitro. Chronically administering progesterone had no effect on adenyl cyclase activity. Hypophysectomy failed to antagonize the stimulatory effect of ovariectomy and also failed to alter the inhibitory effects of estrogen treatment, indicating that estrogens do not act via release of gonadotropins. Nor...