scholarly journals Second-messenger systems underlying amine and peptide actions on cardiac muscle in the horseshoe crab Limulus polyphemus

1989 ◽  
Vol 145 (1) ◽  
pp. 419-437 ◽  
Author(s):  
J. R. Groome ◽  
W. H. Watson
Keyword(s):  
Cyclic Amp ◽  
Cardiac Muscle ◽  
Cyclic Gmp ◽  
Phosphodiesterase Inhibitor ◽  
Second Messenger ◽  
Muscle Contractility ◽  
Contraction Amplitude ◽  
Second Messenger Systems ◽  
Biochemical Mechanisms ◽  
Cardiac Muscle Fibers

The biochemical mechanisms by which octopamine, catecholamines and the peptide proctolin exert their actions on Limulus cardiac muscle were investigated. Amines produced long-lasting increases in the amplitude of contractions evoked by electrical stimulation. At 10(−5) mol l-1, the apparent order of potency for amine-induced increases in evoked contraction amplitude was dopamine approximately equal to octopamine greater than norepinephrine approximately equal to epinephrine. At this dose, amines produced long-lasting increases in the levels of cyclic AMP (octopamine greater than dopamine approximately equal to norepinephrine approximately equal to epinephrine), but not of cyclic GMP, in Limulus cardiac muscle. Like the amines, the adenylate cyclase activator forskolin enhanced cardiac muscle contractility and increased levels of cyclic AMP, but not of cyclic GMP. The phosphodiesterase inhibitor IBMX produced a transient increase in cardiac muscle contractility, but typically produced long-lasting negative inotropy. This agent increased levels of both cyclic AMP and cyclic GMP in Limulus cardiac muscle. Proctolin and the protein kinase C activator phorbol dB increased the contraction amplitude of the intact heart and the electrically stimulated myocardium. These compounds, as well as dopamine, elicited sustained contractures and rhythmic contractions when applied to deganglionated Limulus cardiac muscle rings. Unlike the amines, proctolin and phorbol dB did not increase cardiac muscle cyclic AMP levels. These results suggest that several second-messenger systems may be utilized by amines and peptides to produce excitatory actions on cardiac muscle fibers of the Limulus heart. Cyclic AMP appears to be an important second messenger underlying the effects of amines to enhance cardiac muscle contractility. Pharmacological data suggest that proctolin may alter cardiac muscle contractility and excitability by a mechanism which involves the phosphatidylinositol pathway. Dopamine, unlike the other amines, produces a number of proctolin-like effects and may activate both the cyclic AMP and the phosphatidylinositol systems in Limulus cardiac muscle.

scholarly journals Effect of buffer composition on binding of adenosine 3′:5′-cyclic monophosphate by bovine adrenal extracts

1977 ◽  
Vol 166 (3) ◽  
pp. 553-557 ◽  
Author(s):  
J Linkola ◽  
F Fyhrquist ◽  
T H Weber ◽  
L Puutula
Keyword(s):  
Environmental Factors ◽  
Cyclic Amp ◽  
Binding Affinity ◽  
Cyclic Gmp ◽  
Disodium Salt ◽  
Binding Material ◽  
Second Messenger Systems ◽  
Buffer Composition ◽  
Fold Excess ◽  
High Binding Affinity

The binding of cyclic [3H] AMP by bovine adrenal extracts was studied in different buffer systems; 50 mM-Tris/HCl, pH 7.5, buffer containing 4mM-EDTA (disodium salt) offered advantages such as low non-specific interference and high binding affinity. 2-Mercaptoethanol decreased, but EDTA and theophylline increased, the specificity of cyclic [3H]AMP binding as expressed by the displacement of cyclic [3H]AMP by a 1000-fold excess of unlabelled cyclic GMP. The study indicated heterogeneity of the binding material. Mg2+-dependent binding may be eliminated in Tris/EDTA buffer. The heterogeneity and the specificity of intracellular cyclic AMP binders and their dependence in environmental factors should be considered in the evaluation of cyclic AMP binding and second-messenger systems.

scholarly journals Evidence for the involvement of cyclic AMP in the pheromonal modulation of barnacle settlement

1995 ◽  
Vol 198 (3) ◽  
pp. 655-664 ◽  
Author(s):  
A Clare ◽  
R Thomas ◽  
D Rittschof
Keyword(s):  
Signal Transduction ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclic Gmp ◽  
Phosphodiesterase Inhibitor ◽  
Balanus Amphitrite ◽  
Dibutyryl Cyclic Amp ◽  
Physico Chemical ◽  
Miconazole Nitrate

The involvement of cyclic AMP in the settlement of the cypris larva of Balanus amphitrite amphitrite Darwin has been examined through the use of compounds that affect intracellular cyclic AMP levels. The activation of adenylate cyclase with forskolin, and the inhibition of phosphodiesterase with 3-isobutyl-1-methylxanthine, caffeine and theophylline, significantly increased the settlement of cyprids. Although the analogue dibutyryl cyclic AMP appeared to increase settlement, the effect was not significant. No marked increase in settlement resulted from the incubation of cyprids with dibutyryl cyclic GMP, 8-(4-chlorophenylthio) (CPT) cyclic AMP or papaverine (a phosphodiesterase inhibitor). Miconazole nitrate, an adenylate cyclase inhibitor, prevented settlement, but this effect appeared to be physico-chemical rather than pharmacological. Radioimmunoassay did not clearly show whether cyclic AMP levels changed following exposure of cyprids to a pulse of crude barnacle extract. However, exposure to forskolin significantly increased the cyclic AMP titre of cyprids. We conclude that compounds that alter intracellular cyclic AMP levels alter normal patterns of cyprid settlement. Whether this is because of an alteration in signal transduction is unclear.

Role of cyclic AMP in regulating cardiac muscle contractility: Novel pharmacological approaches to modulating cyclic AMP degradation by phosphodiesterase

1988 ◽  
Vol 12 (2) ◽  
pp. 119-129 ◽  
Author(s):  
Ronald E. Weishaar ◽  
Dianne C. Kobylarz-Singer ◽  
Mary M. Quade ◽  
Harvey R. Kaplan
Keyword(s):  
Cyclic Amp ◽  
Cardiac Muscle ◽  
Muscle Contractility

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.

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