scholarly journals Involvement of cyclic AMP in multiple, excitatory actions of biogenic amines on the cardiac ganglion of the horseshoe crab Limulus polyphemus

1990 ◽  
Vol 152 (1) ◽  
pp. 313-331
Author(s):  
J. R. Groome ◽  
W. H. Watson
Keyword(s):  
Cyclic Amp ◽  
Biogenic Amines ◽  
Time Course ◽  
Phosphodiesterase Inhibitor ◽  
Nucleotide Metabolism ◽  
Muscle Fibres ◽  
Cardiac Ganglion ◽  
Biochemical Effect ◽  
Pharmacological Agents ◽  
Dose Dependent

Cyclic AMP appears to be involved in several excitatory actions of amines on neurones of the Limulus cardiac ganglion. Amines selectively increase levels of cardiac ganglion cyclic AMP with a magnitude and time course similar to that observed for amine-induced excitation of cardiac ganglion burst rate. With respect to either the physiological or biochemical effect, the apparent order of potency is octopamine greater than epinephrine approximately dopamine greater than norepinephrine. Elevation of cardiac ganglion cyclic AMP levels by octopamine or dopamine is dose-dependent and is potentiated by the phosphodiesterase inhibitor 3-isobutyl 1-methylxanthine (IBMX). Several pharmacological agents which influence cyclic nucleotide metabolism, including forskolin, IBMX and 8-substituted cyclic AMP analogues, have amine-like effects on the Limulus cardiac ganglion. These effects include increased burst rate of the isolated cardiac ganglion and decreased burst duration, interburst interval and number of spikes per burst in follower neurones. Forskolin and IBMX increase levels of cardiac ganglion cyclic AMP, and IBMX also increases cyclic GMP levels in this tissue. Amines, forskolin and IBMX have direct effects on follower neurones pharmacologically isolated from pacemaker cell input. Octopamine, forskolin and IBMX depolarize follower neurones, while dopamine hyperpolarizes these cells. Amines, forskolin and IBMX elicit burst-like potentials in follower neurones, and increase the size of evoked, unitary junction potentials recorded in cardiac muscle fibres. These pharmacological and biochemical data suggest that multiple, excitatory effects of biogenic amines on the Limulus cardiac ganglion are mediated by simultaneous increases in cyclic AMP at several loci within this neural network.

Cyclic AMP Mediates Serotonin-Induced Synaptic Enhancement of Lateral Giant Interneuron of the Crayfish

2005 ◽  
Vol 94 (4) ◽  
pp. 2644-2652 ◽  
Author(s):  
Makoto Araki ◽  
Toshiki Nagayama ◽  
Jordanna Sprayberry
Keyword(s):  
Biogenic Amines ◽  
Time Course ◽  
Neural Circuit ◽  
Escape Behavior ◽  
Direct Injection ◽  
Phosphodiesterase Inhibitor ◽  
Sensory Stimulation ◽  
Simultaneous Application ◽  
Camp Analogue ◽  
Repetitive Sensory Stimulation

The lateral giant (LG)-mediated escape behavior of the crayfish habituates readily on repetitive sensory stimulation. Recent studies suggested that the biogenic amines serotonin and octopamine modulate the time course of recovery and/or re-depression of the LG response after habituation. However, little is known of how serotonin and octopamine effect LG habituation and what second-messenger cascades they may activate. To investigate the effect of biogenic amines on LG habituation, serotonin and octopamine were superfused before presenting repetitive sensory stimulation. Serotonin and octopamine increased the number of stimuli needed to habituate the LG response. Their effects were mimicked by mixed application of a cAMP analogue [8-(4-chlorophenylthio)-cAMP (CPT-cAMP)] and a phosphodiesterase inhibitor [3-isobutyl-1-methylxanthine (IBMX)] but not by a cGMP analogue (8-bromoguanosine 3′,5′-cyclic monophosphate). Perfusion of the adenylate cyclase inhibitor (SQ22536) abolished the effect of serotonin but not that of octopamine. To investigate the site of action of each biogenic amines in the neural circuit meditating LG escape, the effect of drugs on directly and indirectly elicited postsynaptic potentials in LG was investigated. Serotonin, octopamine, and a mixture of CPT-cAMP and IBMX increased both the direct and indirect synaptic inputs. Simultaneous application of SQ22536 abolished the effect of serotonin on both inputs but did not block the effect of octopamine. Direct injection of the cAMP analogue (Sp-isomer of adenosine-3′,5′-cyclic monophosphorothioate) into LG increased both the direct and indirect inputs to LG. These results indicate that serotonin mediates an increase in cAMP levels in LG, but octopamine acts independently of cAMP and cGMP.

Dexamethasone and 8-bromo-cyclic AMP depress the incorporation of [3H]thymidine into mouse condylar cartilage by different pathways

1986 ◽  
Vol 109 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Z. Kraiem ◽  
G. Maor ◽  
M. Silbermann
Keyword(s):  
Cyclic Amp ◽  
Thymidine Incorporation ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Condylar Cartilage ◽  
Camp Analogue ◽  
Dose Dependent Fashion ◽  
Cartilage Cells ◽  
Dose Dependent

ABSTRACT We examined whether cyclic AMP (cAMP) affects the incorporation of [3H]thymidine into cartilage cells and, if so, whether this action could be related to the inhibitory effect of glucocorticoid hormones on the growth of ossifying cartilage. Incorporation of [3H]thymidine into trichloroacetic acid-precipitable material by mouse cartilage was measured concomitantly with the concentration of cAMP. Dexamethasone (1 μmol/l) significantly (P < 0·05) depressed the incorporation of [3H]thymidine. The cAMP analogue 8-bromo-cAMP (0·01–1 mmol/l) also depressed the incorporation of the radionucleotide in a dose-dependent fashion. When various concentrations of 8-bromo-cAMP were added with dexamethasone (1 μmol/l), no apparent changes took place compared with the effect of dexamethasone alone. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0·2-1 mmol/l) elicited an inhibitory effect on [3H]thymidine incorporation and a stimulatory influence on cartilage cAMP concentrations. Dexamethasone, at doses (0·01–1 μmol/l) causing significant inhibition of [3H]thymidine incorporation, failed to increase cartilage levels of cAMP. It seems, therefore, that the depressive effect of dexamethasone on [3H]thymidine incorporation in condylar cartilage is not mediated through an increase of cAMP in the tissue. J. Endocr. (1986) 109, 209–213

Regulation of Thromboplastin Synthesis in Mouse Placental Cells In Vitro

1983 ◽  
Vol 50 (04) ◽  
pp. 831-834 ◽  
Author(s):  
Knut Dalaker ◽  
Hans Prydz
Keyword(s):  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Low Concentrations ◽  
Placental Cells ◽  
Dose Dependent ◽  
Higher Doses ◽  
Dose Dependent Effect ◽  
Methyl Xanthine

SummaryMouse placental cells are probably constitutive producers of the thromboplastin apoprotein in vitro. The effect of cyclic AMP- elevating compounds on their expression of thromboplastin activity has been studied. Dibutyryl cyclic AMP, the phosphodiesterase inhibitor Ro 20-1724 and the adenyl cyclase stimulator forskolin all decrease the synthesis of thromboplastin. Prostaglandin E2 and the phosphodiesterase inhibitor butyl-methyl-xanthine have a biphasic dose dependent effect. A stimulation was observed at low concentrations, whereas higher doses decreased the synthesis of thromboplastin. Adrenaline had no effect. Combination of two compounds, each at maximally inhibiting concentration gave no significant additive inhibitory effect, showing that they probably act via the same pathway.

scholarly journals Use of forskolin to study the relationship between cyclic AMP formation and bone resorption in vitro

1986 ◽  
Vol 240 (2) ◽  
pp. 529-539 ◽  
Author(s):  
U H Lerner ◽  
B B Fredholm ◽  
M Ransjö
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Cyclic Amp Accumulation ◽  
The Relationship ◽  
Dose Dependent ◽  
Old Mice ◽  
45Ca Release

The effect of the adenylate cyclase activator forskolin on bone resorption and cyclic AMP accumulation was studied in an organ-culture system by using calvarial bones from 6-7-day-old mice. Forskolin caused a rapid and fully reversible increase of cyclic AMP, which was maximal after 20-30 min. The phosphodiesterase inhibitor rolipram (30 mumol/l), enhanced the cyclic AMP response to forskolin (50 mumol/l) from a net cyclic AMP response of 1234 +/- 154 pmol/bone to 2854 +/- 193 pmol/bone (mean +/- S.E.M., n = 4). The cyclic AMP level in bones treated with forskolin (30 mumol/l) was significantly increased after 24 h of culture. Forskolin, at and above 0.3 mumol/l, in the absence and the presence of rolipram (30 mumol/l), caused a dose-dependent cyclic AMP accumulation with an calculated EC50 (concentration producing half-maximal stimulation) value at 8.3 mumol/l. In 24 h cultures forskolin inhibited spontaneous and PTH (parathyroid hormone)-stimulated 45Ca release with calculated IC50 (concentration producing half-maximal inhibition) values at 1.6 and 0.6 mumol/l respectively. Forskolin significantly inhibited the release of 3H from [3H]proline-labelled bones stimulated by PTH (10 nmol/l). The inhibitory effect by forskolin on PTH-stimulated 45Ca release was significant already after 3 h of culture. In 24 h cultures forskolin (3 mumol/l) significantly inhibited 45Ca release also from bones stimulated by prostaglandin E2 (1 mumol/l) and 1 alpha-hydroxycholecalciferol (0.1 mumol/l). The inhibitory effect of forskolin on spontaneous and PTH-stimulated 45Ca release was transient. A dose-dependent stimulation of basal 45Ca release was seen in 120 h cultures, at and above 3 nmol of forskolin/l, with a calculated EC50 value at 16 nmol/l. The stimulatory effect of forskolin (1 mumol/l) could be inhibited by calcitonin (0.1 unit/ml), but was insensitive to indomethacin (1 mumol/l). Forskolin increased the release of 3H from [3H]proline-labelled bones cultured for 120 h and decreased the amount of hydroxyproline in bones after culture. Forskolin inhibited PTH-stimulated release of Ca2+, Pi, beta-glucuronidase and beta-N-acetylglucosaminidase in 24 h cultures. In 120 h cultures forskolin stimulated the basal release of minerals and lysosomal enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Resensitization of hepatocyte glucagon-stimulated adenylate cyclase can be inhibited when cyclic AMP phosphodiesterase inhibitors are used to elevate intracellular cyclic AMP concentrations to supraphysiological values

1988 ◽  
Vol 249 (2) ◽  
pp. 543-547 ◽  
Author(s):  
G J Murphy ◽  
M D Houslay
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Phosphodiesterase Inhibitor ◽  
Phosphodiesterase Inhibitors ◽  
Maximal Effect ◽  
Cyclic Amp Phosphodiesterase ◽  
Dose Dependent Fashion ◽  
Independent Process ◽  
Pre Treatment ◽  
Dose Dependent

Treatment of intact hepatocytes with glucagon led to the rapid desensitization of adenylate cyclase, which reached a maximum around 5 min after application of glucagon, after which resensitization ensued. Complete resensitization occurred some 20 min after the addition of glucagon. In hepatocytes which had been preincubated with the cyclic AMP phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), glucagon elicited a stable desensitized state where resensitization failed to occur even 20 min after exposure of hepatocytes to glucagon. Treatment with IBMX alone did not elicit desensitization. The action of IBMX in stabilizing the glucagon-mediated desensitized state was mimicked by the non-methylxanthine cyclic AMP phosphodiesterase inhibitor Ro-20-1724 [4-(3-butoxy-4-methoxylbenzyl)-2-imidazolidinone]. IBMX inhibited the resensitization process in a dose-dependent fashion with an EC50 (concn. giving 50% of maximal effect) of 26 +/- 5 microM, which was similar to the EC50 value of 22 +/- 6 microM observed for the ability of IBMX to augment the glucagon-stimulated rise in intracellular cyclic AMP concentrations. Pre-treatment of hepatocytes with IBMX did not alter the ability of either angiotensin or the glucagon analogue TH-glucagon, ligands which did not increase intracellular cyclic AMP concentrations, to cause the rapid desensitization and subsequent resensitization of adenylate cyclase. It is suggested that, although desensitization of glucagon-stimulated adenylate cyclase is elicited by a cyclic AMP-independent process, the resensitization of adenylate cyclase can be inhibited by a process which is dependent on elevated cyclic AMP concentrations. This action can be detected by attenuating the degradation of cyclic AMP by using inhibitors of cyclic AMP phosphodiesterase.

Theophylline Inhibition of Nucleoside Transport and its Relation to Cyclic AMP in Skeletal Muscle

1974 ◽  
Vol 52 (6) ◽  
pp. 1063-1073 ◽  
Author(s):  
Yin-Tak Woo ◽  
J. F. Manery ◽  
E. E. Dryden
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Amp ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Nucleoside Transport ◽  
Intracellular Uptake ◽  
Frog Skeletal Muscle ◽  
Dibutyryl Cyclic Amp ◽  
Cyclic Amp Phosphodiesterase ◽  
Dose Dependent

Using [14C]inosine and [3H]sorbitol, the effect of theophylline on inosine uptake was studied. Theophylline inhibited the intracellular uptake of inosine by isolated, frog skeletal muscle in a dose-dependent way. An inhibitory effect was also observed for the uptake of labelled adenosine, uridine, hypoxanthine, and adenine, but not for ribose. The inhibition was not readily reversible and was noncompetitive in nature. It was not secondary to the contracture of the muscle produced by the drug, because various treatments known to cause contracture had no effect on inosine transport. Also, papaverine (0.3 mM) significantly inhibited inosine transport without affecting the contractile properties of the muscle. Although theophylline is a cyclic AMP phosphodiesterase inhibitor, no relation could be found between inhibition of inosine uptake and cyclic AMP. N8,O2′-Dibutyryl cyclic AMP (1 mM) was ineffective. Though isoproterenol (10 μg/ml) increased the cyclic AMP concentrations in the muscle by 26-fold in the presence of theophylline and 3-fold in the absence of the drug, it did not influence inosine transport. Tracing the label into various intracellular nucleotides after incubation of the muscle with [14C]inosine suggested that theophylline inhibited inosine transport rather than inosine metabolism.

Effects of suboptimal levels of extracellular calcium on the regulation of the cyclic AMP phosphodiesterase-inhibitor system and membrane differentiation in Dictyostelium discoideum

1988 ◽  
Vol 90 (4) ◽  
pp. 691-700 ◽  
Author(s):  
M.B. Coukell ◽  
A.M. Cameron
Keyword(s):  
Cyclic Amp ◽  
Dictyostelium Discoideum ◽  
Cyclic Gmp ◽  
Phosphodiesterase Inhibitor ◽  
Wild Type ◽  
Cyclic Amp Phosphodiesterase ◽  
Dose Dependent Fashion ◽  
Inhibitor System ◽  
Membrane Bound ◽  
Dose Dependent

When starved wild-type amoebae of Dictyostelium discoideum were washed and incubated in 1 mM-EGTA, their ability to induce soluble cyclic AMP phosphodiesterase (PD) activity in response to either millimolar cyclic AMP or a series of nanomolar cyclic AMP pulses was reduced by 55–75%. Supplementation of EGTA-treated cells with exogenous Ca2+ stimulated PD induction in a dose-dependent fashion (EC50 = 100–200 nM free extracellular Ca2+), and enzyme production was maximal at about 1 microM free Ca2+. Ca2+ depletion also strongly impaired production of the phosphodiesterase inhibitor (PDI). In contrast, other than delaying their appearance by about 1 h, EGTA had little effect on the induction by cyclic AMP pulses of cell surface markers such as contact sites A and membrane-bound PD activity. Similar changes in both the soluble and membrane activities were observed with strain NP368, a mutant that overproduces cyclic GMP when stimulated by cyclic AMP. Thus, Ca2+ depletion does not appear to inhibit PD and PDI production by reducing intracellular cyclic GMP. To determine whether Ca2+ depletion alters signal transduction, two mutants that produce the soluble PD activities constitutively were examined. Suboptimal concentrations of free extracellular Ca2+ were found to inhibit PD production in these cells to the same degree and with the same concentration dependence as low Ca2+ inhibited PD induction by cyclic AMP in wild-type cells. These results suggest that Ca2+ depletion by EGTA probably inhibits PD and PDI production indirectly by perturbing an intracellular Ca2+ pool(s) rather than by altering a surface cyclic AMP-receptor-mediated process.

Prolongation of the effects of gonadotrophins and prostaglandin E2 on ovarian cyclic AMP formation by inhibitors of protein synthesis

1980 ◽  
Vol 94 (2) ◽  
pp. 251-258 ◽  
Author(s):  
Christina Bergh ◽  
Kurt Ahrén
Keyword(s):  
Protein Synthesis ◽  
Cyclic Amp ◽  
Time Course ◽  
Phosphodiesterase Inhibitor ◽  
Specific Protein ◽  
Early Effect ◽  
Old Rats ◽  
Turn Over ◽  
Initial Peak ◽  
Whole Ovaries

Abstract. The effects of LH, FSH and PGE2 on the accumulation of cyclic AMP by isolated whole ovaries from 23–24 day-old rats were studied in time-course experiments in presence and absence of two inhibitors of protein synthesis, puromycin and cycloheximide. In absence of these inhibitors ovarian cyclic AMP levels reached peak levels within 30 min for all three stimulators and returned towards pre-stimulation levels within 2–4 h. When puromycin (500 μg/ml) or cycloheximide (5 μg/ml) was present together with LH, FSH or PGE2, respectively, ovarian cyclic AMP levels did not decrease after the initial peak but remained high for the entire incubation period (4–5 h). The release of cyclic AMP to the incubation medium was also much higher when puromcyin or cycloheximide was present, illustrating that the effect of puromycin and cycloheximide was not caused by an inhibition of the cyclic AMP release. The effects of puromycin and cycloheximide were, in principle, the same when a phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine, was present. The results indicate either that there are, in the ovary, proteins with very rapid turn-over, necessary for the mechanism leading to refractoriness of the cyclic AMP system, or that the gonadotrophins and PGF2 as an early effect stimulate the production of a specific protein necessary for the development of refractoriness.

scholarly journals Changes in cyclic AMP and cyclic GMP concentrations during the action of 5-hydroxytryptamine on an insect salivary gland

1980 ◽  
Vol 192 (1) ◽  
pp. 247-255 ◽  
Author(s):  
J P Heslop ◽  
M J Berridge
Keyword(s):  
Salivary Gland ◽  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Time Course ◽  
Phosphodiesterase Inhibitor ◽  
Fluid Secretion ◽  
Fast Response ◽  
Bathing Medium ◽  
Calliphora Erythrocephala

Salivary glands from adult blowflies (Calliphora erythrocephala Meigen) were studied in vitro. The time course of changes in cyclic AMP content of the glands was followed at different concentration of 5-hydroxytryptamine. There was an immediate biphasic rise and fall in cyclic AMP content, following by a slower rise and subsequent gradual decline. The initial rise preceded the onset of fluid secretion by the glands. Rises in cyclic AMP content were inhibited by compound RMI 12330 A (an adenylate cyclase inhibitor) and were halted after about 15-20s if the glands were deprived of Ca2+. Theophylline (a phosphodiesterase inhibitor) abolished the decline phase of the fast response, Losses of cyclic AMP from the glands either to the bathing medium or to the saliva were small and could not account for the rapid fall found. Evidence is presented that cyclic GMP is not involved in the process of initiating secretion in the blowfly salivary gland.

INTERACTION OF THYROID-STIMULATING ANTIBODIES WITH THE HUMAN THYROTROPHIN RECEPTOR

1977 ◽  
Vol 75 (3) ◽  
pp. 401-407 ◽  
Author(s):  
B. REES SMITH ◽  
GWYNETH A. PYLE ◽  
V. B. PETERSEN ◽  
R. HALL
Keyword(s):  
Cyclic Amp ◽  
Time Course ◽  
Receptor Site ◽  
Kinetic Studies ◽  
Dependent Manner ◽  
Similar Time ◽  
Thyroid Stimulating Antibodies ◽  
Binding Data ◽  
Rate Limiting ◽  
Dose Dependent

Thyroid-stimulating antibodies (TSAb) were found to inhibit the binding of labelled thyrotrophin (TSH) to thyroid membranes in a dose-dependent manner and this effect was localized in the Fab part of the TSAb molecule. Analysis of the binding data suggested that TSAb and TSH bound to the same receptor site. Production of cyclic AMP by the thyroid membranes was stimulated by TSAb and TSAb–Fab with a similar time course to that observed with TSH. Kinetic studies indicated that the binding of TSAb to the thyroid membranes was not rate-limiting in the process of stimulation of cyclic AMP production.

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