Alterations in the levels of cAMP and cGMP after decentralization of the rat superior cervical ganglion.

After cutting the preganglionic nerve trunk of the rat's superior cervical ganglion, the levels of cAMP and cGMP were measured in a postoperative period of between 3 and 21 dad by a partial recovery after 7 to 21 days.     

Early changes of cyclic nucleotide levels in a mitogenic reaction in the rat mesentery.

By measuring simultaneously cAMP and cGMP we found a biphasic time course with regard to cGMP and the cGMP/cAMP ratio very early in a mitogenic reaction in vivo. This is a new finding.     

Early changes of cyclic nucleotide levels in a mitogenic reaction in the rat mesentery

Summary By measuring simultaneously cAMP and cGMP we found a biphasic time course with regard to cGMP and the cGMP/cAMP ratio very early in a mitogenic reaction in vivo. This is a new finding.This work was supported by the Swedish Cancer Society and the Swedish Medical Research Council (project No. 04X-04498). We are indebted to Marcela Bartonek and Margareta Odenö for expert technical assistance and to Erik Leander for help with statistical matters.     

Changes in the activities of protein kinase modulators in the cerebellum of mice due to ethanol, caffeine, or phenobarbital administration.

Decreased activities of both the inhibitory modulator of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase (A-PK) as well as the stimulatory modulator of guanosine 3':5'-monophosphate (cGMP)-dependent protein kinase (G-PK) from the mouse cerebellum were noted due to the administration of excessive doses of ethanol, caffeine, and phenobarbital for up to 28 days. The dose-dependent of the inhibition of A-PK or the stimulation of G-PK was observed as a function of the amount of protein kinase modulators in the cerebellum of mice receiving different doses of ethanol.     

Further investigations on the trophic effect of 3′∶5′-cyclic adenosine monophosphate and 3′∶5′-cyclic guanosine monophosphate on the zona glomerulosa of hypophysectomized rat adrenal cortex

Riassunto Oltre il cAMP, anche il cGMP esercita azione trofica sulla zona glomerulare di ratto. Entrambi i nucleotidi ciclici però, anche se somministrati in alte dosi, non annullano completamente glieffetti dell'ipofisectomia. La somministrazione simultanea di cAMP a cGMP provoca, invece, pieno mantenimento del trofismo della zona glomerulare di ratto ipofisectomizzato. Viene discussa la possibilità che entrambi i nucleotidi ciclici intervengano nella mediazione intracellulare dell'azione glomerulotrofica dell'ACTH.     

Transduction of the chemotactic cAMP signal across the plasma membrane ofDictyostelium cells

AggregatingDictyostelium cells secrete cAMP during cell aggregation. cAMP induces two fast responses, the production of more cAMP (relay) and directed cell locomotion (chemotaxis). Extracellular cAMP binds to G-protein-coupled receptors leading to the activation of second messenger pathways, including the activation of adenylyl cyclase, guanylyl cyclase, phospholipase C and the opening of plasma membrane Ca²⁺ channels. Many genes encoding these sensory transduction proteins have been cloned and null mutants of nearly all components have been characterized in detail. Undoubtedly, activation of adenylyl cyclase is the most complex, involving G-proteins, a soluble protein called CRAC and components of the MAP kinase pathway. Null mutants in this pathway do not aggregate, but can exhibit chemotaxis and develop normally when supplied with exogenous cAMP. The pathways leading to the activation of phospholipase C were identified, but unexpectedly, deletion of the phospholipase C gene has no effect on chemotaxis and development, nor on intracellular Ins(1,4,5)P₃ levels; the metabolism of this second messenger will be discussed in some detail. Activation of guanylyl cyclase is G-protein-dependent and essential for chemotaxis. Analysis of a collection of chemotactic mutants reveals that most mutants are defective in either the production or intracellular detection of cGMP, thereby placing this second messenger at the center of chemotactic signal transduction. Analysis of the cAMP-mediated opening of plasma membrane calcium channels in signal transduction mutants suggests that it has two components, one that depends on G-proteins and intracellular cGMP and one that is G-protein-independent.     

The inhibitory effect of paraquat on histamine and isoproterenol induced changes of cyclic nucleotides in rat lung slices.

The incubation of rat lung slices with paraquat ion (10(-4) M) had no effect on cAMP and cGMP levels of the rat lung slices. The preincubation with the same concentration of paraquat inhibited the cAMP elevating effect of histamine (10(-5) M) and isoproterenol (10(-5) M) and reduced the cGMP level to approximately 50% of the level obtained without preincubation with paraquat.     

Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities.

Carbenoxolone inhibited in vitro cAMP and cGMP phosphodiesterases in a concentration-dependent and noncompetitive manner. Prostaglandin synthetase activity of rabbit kidney medulla was slightly stimulated by carbenoxolone 0.1--0.5 mM, but inhibited by higher concentrations.     

Rosette formation by human T and B lymphocytes in the presence of adrenergic and cholinergic drugs.

It was shown that adrenergic drugs, which increase the intracellular levels of cAMP, inhibit the rosette formation by T-lymphocytes, but stimulate the rosettes produced by B-lymphocytes. Cholinergic drugs, which increase the levels of cGMP, on the contrary, stimulate the formation of rosettes by T-lymphocytes but inhibit those produced by B-lymphocytes.     

The inhibitory effect of paraquat on histamine and isoproterenol induced changes of cyclic nucleotides in rat lung slices

Summary The incubation of rat lung slices with paraquat ion (10^–4 M) had no effect on cAMP and cGMP levels of the rat lung slices. The preincubation with the same concentration of paraquat inhibited the cAMP elevating effect of histamine (10^–5 M) and isoproterenol (10^–5 M) and reduced the cGMP level to approximately 50% of the level obtained without preincubation with paraquat.This work was supported by the Research Grant No. 5 R01 HL 19720-03 from NHLI Department of Health, Education and Welfare, Washington, D.C.     

Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities

Summary Carbenoxolone inhibited in vitro cAMP and cGMP phosphodiesterases in a concentration-dependent and noncompetitive manner. Prostaglandin synthetase activity of rabbit kidney medulla was slightly stimulated by carbenoxolone 0.1–0.5 mM, but inhibited by higher concentrations.Acknowledgment. Supported by a grant from the Orion and Medica Scientific Foundation, Finland.     

Intracellular injection of cAMP and cGMP into snail neurones induces an increase in Na+-conductance

Injection of cAMP and more rarely cGMP into the neurones of the snail Helix pomatia induces an increase in membrane conductance, membrane depolarization and excitation. The effect is theophylline-dependent and has a reversal potential near -10mV.     

An assessment of the effect of hormone and neurotransmitters on adenine and guanine derivatives simultaneously in rat brain cortical slices.

A A 2-dimensional thin-layer method has been developed for the separation on cellulose of adenine and guanine derivatives. Using incubated rat cerebral cortex slices it was shown that noradrenaline and acetylcholine stimulated cAMP and cGMP production respectively but glutamate and gamma-aminobutyric acid stimulated production of both cyclic nucleotides.     

Effects of adrenergic and cholinergic agonists on adenylate and guanylate cyclase activity of isolated guinea-pig seminal vesicle epithelium.

Isolated seminal vesicle epithelium of the guinea-pig contained increased amounts of cAMP and cGMP after treatment with PGE1 and carbachol, respectively. Adrenergic agents had no influence. Possible physiological implications of these results are discussed.     

Rosette formation by human T and B lymphocytes in the presence of adrenergic and cholinergic drugs

Summary It was shown that adrenergic drugs, which increase the intracellular levels of cAMP, inhibit the rosette formation by T-lymphocytes, but stimulate the rosettes produced by B-lymphocytes. Cholinergic drugs, which increase the levels of cGMP, on the contrary, stimulate the formation of rosettes by T-lymphocytes but inhibit those produced by B-lymphocytes.Acknowledgments. This investigation was supported by Grant from National Council for Scientific and Technological Development (CNPq), Rio de Janeiro, Brazil.     

Hormonal control of mammalian oocyte meiosis at diplotene stage

Mammalian oocytes grow and undergo meiosis within ovarian follicles. Fully grown oocytes are arrested at the first meiotic prophase by a mural granulosa origin “arrester” until a surge of luteinizing hormone (LH) from the pituitary at the mid-cycle stimulates the immature oocyte to resume meiosis. Recent evidence indicates that natriuretic peptide precursor type C (NPPC) produced by mural granulosa cells stimulates the generation of cyclic guanosine 3′,5′-monophosphate (cGMP) by cumulus cell natriuretic peptide receptor 2 (NPR2), which diffuses into oocyte via gap junctions and inhibits oocyte phosphodiesterase 3A (PDE3A) activity and cyclic adenosine 3′,5′-monophosphate (cAMP) hydrolysis and maintains meiotic arrest with a high intraoocyte cAMP level. This cAMP is generated through the activity of the Gs G-protein by the G-protein-coupled receptor, GPR3 and GPR12, and adenylyl cyclases (ADCY) endogenous to the oocyte. Further studies suggest that endocrine hormones, such as follicle-stimulating hormone (FSH), LH, 17β-estradiol (E2) and oocyte-derived paracrine factors (ODPFs), participate in oocyte meiosis possibly by the regulation of NPPC and/or NPR2. A detailed investigation of NPPC and NPR2 expression in follicle cells will elucidate the precise molecular mechanisms of gonadotropins, and control the arrest as well as resumption of meiosis.     

Intracellular injection of cAMP and cGMP into snail neurones induces an increase in Na+-conductance

Summary Injection of cAMP and more rarely cGMP into the neurones of the snailHelix pomatia induces an increase in membrane conductance, membrane depolarization and excitation. The effect is theophylline-dependent and has a reversal potential near — 10 mV.     

Brain cyclic nucleotide and energy metabolite responses to subanesthetic and anesthetic concentrations of halothane

Adult rats were exposed to 0.5, 1.0 and 1.5% halothane, delivered in air, for 1 h. Whole brain 3',5'-cyclic adenosine monophosphate (cAMP) of halothane-exposed rats showed only a slight increase relative to control values. 3',5'-Cyclic guanosine monophosphate (cGMP) was increased significantly in halothane-exposed rats, and the response was directly related to the halothane concentrations. Adenosine triphosphate (ATP) and phosphocreatine (PC) remained unchanged relative to control values. Correspondence of these values to apparent discrepancies in the literature is discussed.     

Metabolic requirements for entry of DNA in Branhamella catarrhalis.

Although requirements for transformation in Branhamella catarrhalis are quite complex, DNA synthesis does not appear to be one of these needs, as indicated by the inability of nalidixic acid to interefere with transformation. Exogenous sources of energy, such as cAMP and cGMP also failed to enhance frequency, suggesting cells may actively engage in energy production to achieve uptake of DNA, or lack a transport mechanism for these compounds.     

Metabolic requirements for entry of DNA inBranhamella catarrhalis

Summary Although requirements for transformation inBranhamella catarrhalis are quite complex, DNA synthesis does not appear to be one of these needs, as indicated by the inability of nalidixic acid to interefere with transformation. Exogeneous sources of energy, such as cAMP and cGMP, also failed to enhance frequency, suggesting cells may actively engage in energy production to achieve uptake of DNA, or lack a transport mechanism for these compounds.