Cyclase

About: Cyclase is a research topic. Over the lifetime, 10162 publications have been published within this topic receiving 388566 citations.

Cation and structural requirements for P site-mediated inhibition of adenylate cyclase.

Abstract: The cation and structural requirements of the intracellular inhibitory "P" site of adenylate cyclase were investigated in human platelet membranes, bovine sperm particles, and detergent-solubilized and purified preparations from rat and bovine brain. Sensitivity of adenylate cyclase to P site-mediated inhibition was enhanced by reversible and irreversible activators of the enzyme. The most effective sensitization of the platelet and brain adenylate cyclases was observed with Mn2+ and upon proteolysis with inhibin in the presence of guanosine 5'-O-(3-thiotriphosphate). These resulted in IC50 values for (2',5'dideoxy-adenosine (2',5'-dd-Ado) and 2'-deoxy-3'-AMP of approximately 1-2 microM. The data were consistent with the ideas that P site-mediated inhibition of adenylate cyclase is dependent on divalent cation and is a function of enzyme activity. A number of nucleosides and nucleotides were synthesized and used to define structural requirements for P site-mediated inhibition of a detergent-solubilized adenylate cyclase from rat brain. The data suggest a strict requirement for an intact adenine moiety and a beta-glycosidic linkage for the ribosyl moiety. 2'-Deoxy-and especially 2',5'-dideoxy-ribosyl moieties enhanced sensitivity and a strong preference for phosphate at the 3'-position was exhibited. Substitutions at the 5'-ribose position impaired sensitivity. The order of potency and IC50 values of the more potent adenosine analogs were 2',5'-dideoxy-3'-AMP (congruent to 0.1 microM) greater than 2'-deoxy-3'-AMP (congruent to 1 microM) greater than 2',5'-dd-Ado (congruent to 3 microM) greater than 3'-AMP (congruent to 9 microM) greater than 2'-deoxy-adenosine (congruent to 15 microM) greater than adenosine (congruent to 80 microM). Large substitutions at the 3'-ribose position were tolerated, e.g., dApdN di- and dAp(dN)4 penta-nucleotides and succinyl- and p-fluoro-sulfonyl-benzoyl- moieties. The purified adenylate cyclase from bovine brain was inhibited by P site agonists with IC50 values of 34 and 45 microM for 2'-deoxy-3'-AMP and 2',5'-dd-Ado, respectively. The data imply, first, that the locus of the P site is the catalytic subunit of adenylate cyclase and, second, that the increased sensitivity observed with Mn2+ is due to an effect of the cation on the catalytic subunit. In contrast with adenylate cyclases from other mammalian tissues, the enzyme from bovine sperm exhibited only weak sensitivity to P site agonists; 2'-deoxy-3'-AMP congruent to 2',5'-dd-Ado greater than adenosine, each with IC50 values greater than 1000 microM.(ABSTRACT TRUNCATED AT 400 WORDS)

Steroid Hormones: Effects on Adenyl Cyclase Activity and Adenosine 3',5'-Monophosphate in Target Tissues

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.

Isoproterenol-Induced Cardiac Hypertrophy: Modifications in Characteristics of β-Adrenergic Receptor, Adenylate Cyclase, and Ventricular Contraction

Abstract: Several modifications in characteristics of the β- adrenergic receptor-adenylate cyclase system were observed in the cardiac hypertrophy of the rat produced by chronic isoproterenol treatment. These included 1) a decreased number of β- adrenergic receptors without changes in affinity when assayed by (-).[3H]dihydroalprenolol binding, 2) a decreased ability of 5′-guanylylimidodiphosphate to inhibit displacement by isoproterenol of the bound (-)-[3H]dihydroalprenolol, 3) a decreased sensitivity and magnitude of adenylate cyclase in heart homogenates to isoproterenol stimulation coupled with decreases in basal and NaF-stimulated enzyme activity, 4) a decreased responsiveness of the incubated heart minces to isoproterenol stimulation with respect to cAMP formation, and 5) a decreased contractile force development in ventricular strips in response to isoproterenol. All of the above alterations associated with the isoproterenol-induced cardiomegaly disappeared upon regressio n of hypertrophy. Light and electron...

Lithium inhibition of adrenaline-stimulated adenylate cyclase in humans.

Abstract: LITHIUM is an effective therapeutic agent in the treatment and prevention of the manic phase of manic-depression1, and although known to influence many physiological systems, no specific mechanism has been identified for its efficacy in this illness2 One postulated primary site of Li action is as an inhibitor of hormone-stimulated adenylate cyclase3 Li inhibits the ADH-sensitive adenylate cyclase in kidney4,5, the TSH-sensitive adenylate cyclase in thyroid6,7, the prostaglandin-sensitive adenylate cyclase in human platelets8,9, and the noradrenaline-sensitive adenylate cyclase in rat brain10,11

Effects of Ca++ and prostaglandin E1 on vasopressin activation of renal adenyl cyclase.

Abstract: Adenyl cyclase activity was assayed in crude homogenates of the renal cortex, medulla, and papilla of the golden hamster. The specific activity (moles C-AMP/unit of time per mg protein of tissue) of the enzyme under basal conditions, was greatest in papilla, somewhat lower in medulla, and least in cortex. On an absolute scale, the sensitivity to vasopressin was greater in the medullary and papillary than in the cortical homogenates. In addition, at concentrations of 0.1-1.0 mm, CaCl(2) inhibited the enzyme in the order papilla > medulla > cortex. These results imply the existence of distinct differences in the composition of the adenyl cyclase-receptor complex in various parts of the kidney. We proposed that Ca(++) inhibits the core enzyme directly since at the minimally inhibitory concentration (0.1 mm), CaCl(2) reduced to an equivalent extent (a) basal activity, (b) the response to graded doses of vasopressin (0.5 to 50.0 mU/ml) and (c) the response to maximal stimulatory concentrations of NaF (10 mm). Prostaglandin E(1) (PGE(1) = 10(-7)m) had no effect on either basal adenyl-cyclase activity or the response to 10 mm NaF in medullary and papillary homogenates. 7-Oxa-13-prostynoic acid (10(-4)m) similarly had no effect under basal conditions or on stimulation with NaF in medullary homogenates. Both fatty acids, however, inhibited the enzymic response to vasopressin, particularly at low concentrations of the peptide. The straight-chain fatty acid, 11-eicosanoic acid (10(-7)m), was inactive on basal activity or on the response to vasopressin. The possibility that PGE(1) modifies the coupling mechanism between the core enzyme and the hormone-specific receptor is discussed.