Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins

Catecholamines signal through the beta2-adrenergic receptor by promoting production of the second messenger adenosine 3',5'-monophosphate (cAMP). The magnitude of this signal is restricted by desensitization of the receptors through their binding to beta-arrestins and by cAMP degradation by phosphodiesterase (PDE) enzymes. We show that beta-arrestins coordinate both processes by recruiting PDEs to activated beta2-adrenergic receptors in the plasma membrane of mammalian cells. In doing so, the beta-arrestins limit activation of membrane-associated cAMP-activated protein kinase by simultaneously slowing the rate of cAMP production through receptor desensitization and increasing the rate of its degradation at the membrane.     

Nerve growth factor: relationship to the cyclic AMP system of sensory ganglia

Nerve growth factor and N(6),O(2)' dibutyryl adenosine 3',5'-monophosphate both stimulate neurite elongation by explanted ganglia. However, the addition of nerve growth factor does not lead to increased amounts of adenosine 3',5'-monophosphate in intact ganglia, nor does it stimulate adenylate cyclase activity in broken ganglia cells.     

Failure to confirm cyclic AMP as second messenger for norepinephrine in rat cerebellum

Microiontophoretic applications of adenosine 3',5'-monophosphate (cyclic AMP) to spontaneously active, electrophysiologically identified Purkinje cells of the rat cerebellum failed to mimic the strong depressant action of norepinephrine on the same cells. These findings, in combination with a reevaluation of other studies, cast doubt on the hypothesis that cyclic AMP mediates the depressant actions of norepinephrine in the cerebellum.     

Compartmentalization of cyclic AMP during phagocytosis by human neutrophilic granulocytes

Immunocytochemistry shows that early during phagocytosis of zymosan, adenosine 3',5'-monophosphate (cyclic AMP) appears on the cell surface before the phagosome is internalized. The appearance of cyclic AMP on the cell surface is coincident with that of granule products and regulatory subunit of type I cyclic AMP-dependent protein kinase. Guanosine 3',5'-monophosphate is not associated with the initiation site of phagocytosis, but is observed throughout the granular cytoplasmic region. This sharply localized accumulation of cyclic AMP may serve as a signal for the initiation of phagocytosis.     

Selective reduction of forskolin-stimulated cyclic AMP accumulation by inhibitors of protein synthesis

Inhibiting protein synthesis by incubating C6-2B rat astrocytoma cells with cycloheximide or emetine for periods up to 24 hours caused a progressive decrease in the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) when the cells were challenged for 30 minutes with 100 microM forskolin. In contrast, cholera toxin-stimulated (6 nM, 3 hours) cyclic AMP accumulation was not diminished in cycloheximide-treated cells, and cyclic AMP was only minimally diminished in response to a 30-minute challenge with 10 microM (-)-isoproterenol. These experiments suggest the presence of a previously unrecognized cyclase component, which is essential for forskolin-stimulated cyclic AMP accumulation and has a shorter half-life than the beta-adrenergic receptor, the guanine nucleotide regulatory proteins, or the cyclase catalytic component.     

In vivo inhibition of growth of two hormone-dependent mammary tumors by dibutyryl cyclic AMP

Growth of hormone-dependent rat mammary tumors was arrested in vivo by N(6),O(2)'-dibutyryl cyclic adenosine 3',5'-monophosphate. Estrogen concentration did not change, but acid ribonuclease activity and synthesis increased during treatment with the dibutyryl cyclic nucleotide, as was shown during tumor regression due to hormonal deprivation. Growth arrest, thus, appears to derive from enhanced tissue catabolism.     

Catecholamine and dibutyryl cyclic AMP effects on myosin adenosine triphosphatase in cultured rat heart cells

Catecholamines and dibutyryl adenosine 3', 5'-monophosphate (dibutyryl cyclic AMP) increase the activity of myosin adenosine triphosphatase in cultured rat heart cells. Dichloroisoproterenol, an inhibitor of the beta receptor of the catecholamines, inhibits the action of the catecholamines but not of cyclic AMP.     

Effects of dibutyryl cyclic AMP on restoration of function of damaged sciatic nerve in rats

In two experiments, the sciatic nerve of rats was either crushed or hemisected, and N(6),O(2)-dibutyryl adenosine 3',5'-monophosphate or saline was injected intramuscularly near the site of the lesion. In both types of nerve damage, the sensorimotor functions of animals treated with N(6),O(2)-dibutyryl adenosine 3',5'-monophosphate returned earlier than did those of saline-treated control animals.     

Growth arrest and morphological change of human breast cancer cells by dibutyryl cyclic AMP and L-arginine

The growth in vitro of human breast cancer cells, line MCF-7, was inhibited by a daily supplement of L-arginine (1 milligram per milliliter). Arginine acted synergistically with dibutyryl adenosine 3',5'-monophosphate (cyclic AMP) (10(-6) molar) to enhance the growth inhibitory effect: the cell replication ceased completely within 2 days after treatment. The growth arrest accompanied a change in cell morphology and was preceded by increases in the cellular concentration of cyclic AMP, adenylate cyclase, and type II cyclic AMP-dependent protein kinase activities as well as a decrease of estrogen binding activity. The results suggest that growth of human breast cancer cells is subject to cyclic AMP-mediated regulation and that arginine may play a specific role in this process.     

Increased phosphorylation of myosin light chain kinase after an increase in cyclic AMP in intact smooth muscle

The role of cyclic adenosine monophosphate-mediated phosphorylation of myosin light chain kinase in relaxing smooth muscle was examined. The kinase was immunoprecipitated from tissue extracts and the phosphate content was determined. The addition of forskolin to resting or methacholine-contracted muscles resulted in an increase in myosin light chain kinase phosphorylation of myosin light chain kinase is one of the reactions in the process by which cyclic adenosine monophosphate causes relaxation of smooth muscle.     

Inhibition of O-methyltransferase by catechol and sensitization to epinephrine

Catechol at equimolecular concentration inhibits the inactivation of adrenaline by O-methyltransferase in vitro about 50 percent. The inhibition is probably responsible for the sensitization of smooth muscles to epinephrine by various ortho di- or triphenols.     

Strain differences in rat brain epinephrine synthesis: regulation of alpha-adrenergic receptor number by epinephrine

Inbred tht strains Fischer 344 (F344) and Buffalo (BUF) differ in serveral physiological and behavioral measures. It was found that the activity of adrenomedullary and regional brain phenylethanolamine N-methyltransferase is at least four times higher in F344 rats than in BUF rats; these strain-dependent differences corresponded directly with the epinephrine content of the medulla-pons and hypothalamus. Conversely, alpha-adrenergic receptor density in brain regions containing phenylethanolamine N-methyltransferase is two to three times lower in F344 rats than in BUF rats; alpha-receptors in frontal cortex (a brain region lacking phenylethanolamine N-methyltransferase activity and epinephrine) are similar in both strains. These findings suggest that strain-dependent differences in alpha-receptors are regulated by inherited differences in presynaptic adrenergic neuronal function in different brain regions.     

从冲突走向融合--论中国报告文学的发展与90年代报告文学的成熟

以和合学与系统论的观点考察中国报告文学的发展,认为在文学与政治、作家与时代激烈冲突的20世纪,报告文学始终处于冲突、融合的过程之中,正是它在"新闻性"与"文学性"、"文学性"与"政治性"(理性)、歌颂与暴露以及主旋律与多样化等方面的激烈冲突,报告文学才得以发展、进步,才走向融合、新生.而90年代报告文学的成熟与自觉,正是它遵循其自身内在规律而向前发展的必然结果.