From epinephrine to cyclic AMP

Binding of catecholamines to the beta-adrenergic receptor results in the activation of adenylate cyclase and the intracellular formation of adenosine 3',5'-monophosphate (cAMP). In the past 20 years the events that lead from hormone binding at the cell surface receptor site to the synthesis of cAMP at the inner layer of the membrane have been intensively studied. Signal transduction in this system involves the sequential interaction of the beta-adrenergic receptor with the guanine nucleotide-binding protein (Gs) and the adenylate cyclase catalyst (C). The mechanism of signal transduction from the receptor through Gs to C, as well as the role of the adenylate cyclase inhibitory G protein Gi, is discussed.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Modulation of rod-cone coupling by light

Although electrical coupling between rods and cones in the retina has been assumed to be static, it has now been shown that rod-cone coupling can be strengthened by light. Increment threshold measurements reveal that cone input to rods increases progressively as background light becomes brighter. Current injection into cones produces larger responses in adjacent rods in the presence of background light than in darkness. Weak coupling under dark-adapted conditions facilitates synaptic transmission of small rod signals, and strong coupling under light-adapted conditions enhances transmission of large cone signals.     

反相高效液相色谱法测定小鼠心肌中ATP、ADP和AMP含量及分析

建立同时测定小鼠心肌组织中ATP（三磷酸腺苷）、ADP（二磷酸腺苷）和AMP（一磷酸腺苷）含量的高效液相色谱方法。采用反相高效液相色谱模式,使用SepaxBio-C18（250ram×4．6mmID,μm,200A）色谱柱,以60mmoL·L^-1磷酸二氢钾、60mmoL·L^-1磷酸氢二钾组成的缓冲液（pH=6．68）为流动相等比洗脱,流速：O．6mL·min^-1紫外检测波长为259Nm,带宽为30nm。三种目标组分在10min内实现基线分离,平均加标回收率均在99％以上,线性范围为1-200mg·L^-1检出限分别为20、20、25ng。该法简便、准确,易于移植。     

Modulation of brain reward circuitry by leptin

Leptin, a hormone secreted by fat cells, suppresses food intake and promotes weight loss. To assess the action of this hormone on brain reward circuitry, changes in the rewarding effect of lateral hypothalamic stimulation were measured after leptin administration. At five stimulation sites near the fornix, the effectiveness of the rewarding electrical stimulation was enhanced by chronic food restriction and attenuated by intracerebroventricular infusion of leptin. In contrast, the rewarding effect of stimulating neighboring sites was insensitive to chronic food restriction and was enhanced by leptin in three of four cases. These opposing effects of leptin may mirror complementary changes in the rewarding effects of feeding and of competing behaviors.     

茶叶中AMP的苦味掩盖效果评价及其含量的测定方法

为了研究茶叶内部可能存在的苦味抑制效应,采用定量感官分析法比较了蔗糖、D-葡萄糖酸钠、L-谷氨酸钠、乳酸锌和腺苷-5'-磷酸(AMP)对咖啡因、EGCG(表没食子儿茶素没食子酸酯)和茶汤的苦味掩盖作用.结果表明,低浓度的蔗糖(5 mmol·L-1)、葡萄糖酸钠(5 mmol·L-1)和谷氨酸钠(2 mmol·L-1)对苦味掩盖不明显,在高浓度下这3种物质的苦味掩盖效果明显,但对茶汤滋味的协调性产生不利影响.乳酸锌(0.5～1.5 mmol·L-1)和AMP(0.2～0.6 mmol·L-1)对苦味的掩盖作用均明显,但是乳酸锌即使在低浓度下涩感也较强,加重茶汤涩感;AMP是最为有效的苦味掩盖剂,可有效掩盖茶汤的苦味,且对茶汤滋味协调性没有明显影响.此外,还建立了茶叶中AMP的HPLC测定方法,1/15 mmol·L-1的磷酸盐缓冲体系(pH7.0,含5 mmol·L-1四丁基溴化铵,5%甲醇)为主要流动相,35℃条件下C18柱分离,254 nm测定AMP的方法.茶叶中AMP的含量(0.23～0.32 mg·g-1)尚未达到明显掩盖茶叶自身苦味的水平.     

Resolution of lung inflammation by CD44

Successful repair after tissue injury and inflammation requires resolution of the inflammatory response and removal of extracellular matrix breakdown products. We have examined whether the cell-surface adhesion molecule and hyaluronan receptor CD44 plays a role in resolving lung inflammation. CD44-deficient mice succumb to unremitting inflammation following noninfectious lung injury, characterized by impaired clearance of apoptotic neutrophils, persistent accumulation of hyaluronan fragments at the site of tissue injury, and impaired activation of transforming growth factor-beta1. This phenotype was partially reversed by reconstitution with CD44+ cells, thus demonstrating a critical role for this receptor in resolving lung inflammation.