Pharmacology of the myogenic heart of the pond snail Lymnaea stagnalis

1990 ◽  
Vol 63 (6) ◽  
pp. 1413-1425 ◽  
Author(s):  
K. J. Buckett ◽  
G. J. Dockray ◽  
N. N. Osborne ◽  
P. R. Benjamin
Keyword(s):  
Lymnaea Stagnalis ◽  
Isolated Heart ◽  
Rapid Onset ◽  
Heart Tissue ◽  
Pond Snail ◽  
Low Concentrations ◽  
Other Substances ◽  
Heart Preparation ◽  
High Concentrations ◽  
Alpha Bungarotoxin

1. We have used pharmacologic, immunologic, and biochemical techniques to examine the role of neurochemicals in modulating the myogenic heart of the snail, Lymnaea. 2. 5-HT [high-pressure liquid chromatography (HPLC) and immunocytochemistry], dopamine (HPLC), FMRFamide-related peptides (radioimmunoassay and immunocytochemistry) and substance P-related peptides (immunocytochemistry) were shown to be localized within heart tissue. 3. The pharmacologic actions of these substances on the auricle from an isolated heart preparation were examined together with other putative modulators, acetylcholine (ACh), small cardioactive peptides A and B (SCPA and SCPB), [Arg]8vasotocin (AVT), and Lymnaea native FMRFamide-related peptides [Phe-Met-Arg-Phe-NH2 (FMRFamide), Ser-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (SDPFLRFamide) and Gly-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (GDPFLRFamide)]. 4. The response to each substance could be distinguished by different effect on beat rate, amplitude, and diastolic tonus, as well as by the duration of responses to standard 1-min applications. ACh was inhibitory at low concentrations (threshold less than 10(-10) M) but excitatory at high concentrations (10(-6) M). AVT was alone in producing no dose-dependent response. At high concentrations (10(-4) M), AVT caused a massive tonic contraction and cessation of auricle beat. All other substances examined were excitatory. 5. Antagonists to 5-HT (cinanserin), dopamine (ergonovine), and ACh (alpha-bungarotoxin) were identified. 6. ACh, 5-HT, dopamine, and FMRFamide-related peptides all acted on the auricle at low concentrations, and the rapid onset and short duration of their excitatory effects (ACh inhibitory at low concentrations) suggested that they may have roles as neurotransmitters. SCPA and SCPB were also potent (threshold less than 10(-10) M) but produced long-duration responses suggesting a modulatory or hormonal role.

scholarly journals Inositol-1,4,5-trisphosphate and inositol-1,3,4,5-tetrakisphosphate are second messenger targets for cardioactive neuropeptides encoded on the FMRFamide gene

1999 ◽  
Vol 202 (19) ◽  
pp. 2581-2593 ◽  
Author(s):  
D. Willoughby ◽  
M.S. Yeoman ◽  
P.R. Benjamin
Keyword(s):  
Lymnaea Stagnalis ◽  
Inositol Phosphate ◽  
Isolated Heart ◽  
Beat Frequency ◽  
Heart Tissue ◽  
Heart Beat ◽  
Pond Snail ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Inositol Phosphate Production

This paper examines the importance of the calcium-mobilizing inositol phosphate pathway in mediating the effects of FMRFamide and its gene-related neuropeptides on the myogenic heart beat of the pond snail Lymnaea stagnalis. These peptides are encoded on a single exon of the FMRFamide gene and mediate diverse physiological effects in the isolated heart. The rate of production of inositol-1,4, 5-trisphosphate [Ins(1,4,5)P(3)] and inositol-1,3,4, 5-tetrakisphosphate [Ins(1,3,4,5)P(4)], measured using an HPLC method, were both significantly elevated in a concentration-dependent manner by FMRFamide (and were also elevated by FLRFamide). The threshold for increasing inositol phosphate production was low (100 pmol l(−1)) with a peak response occurring at 1 micromol l(−1) FMRFamide. The shape of the dose-response curve for FMRFamide-induced elevation of heart-beat frequency, obtained in pharmacological experiments on the isolated whole heart, was similar to that for stimulation of inositol phosphate levels in homogenized heart tissue. FMRFamide and Ins(1,4,5)P(3) produced similar effects on the rate of heart beat in permeabilized whole hearts. In addition, the phospholipase C inhibitor, neomycin (2.5 mmol l(−)(1)), blocked the stimulatory effects of FMRFamide on Ins(1, 4,5)P(3) production in heart homogenate, and attenuated the excitatory effects of this neuropeptide in the isolated heart. The ‘isoleucine’ pentapeptides, EFLRIamide and pQFYRIamide, also encoded by the FMRFamide gene, produced no significant effects on inositol phosphate production when applied alone or in combination with FMRFamide. These results suggested that FMRFamide (and FLRFamide), but not EFLRIamide and pQFYRIamide, mediated their main effects on heart beat via the inositol phosphate pathway. The fifth peptide, SEQPDVDDYLRDVVLQSEEPLY (‘SEEPLY’) had no effect when applied alone but appeared to modulate the effects of FMRFamide by delaying the time-to-peak of the Ins(1,4,5)P(3) response from 5 s to 20 s by an unknown mechanism.

Application of high-dose propofol during ischemia improves postischemic function of rat hearts: effects on tissue antioxidant capacity

2004 ◽  
Vol 82 (10) ◽  
pp. 919-926 ◽  
Author(s):  
Zhengyuan Xia ◽  
David V Godin ◽  
David M Ansley
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Capacity ◽  
Functional Recovery ◽  
Isolated Heart ◽  
Cardiac Mechanics ◽  
Heart Tissue ◽  
Global Ischemia ◽  
High Dose ◽  
High Concentration ◽  
Heart Preparation

Previous studies have shown that reactive oxygen species mediated lipid peroxidation in patients undergoing cardiac surgery occurs primarily during cardiopulmonary bypass. We examined whether application of a high concentration of propofol during ischemia could effectively enhance postischemic myocardial functional recovery in the setting of global ischemia and reperfusion in an isolated heart preparation. Hearts were subjected to 40 min of global ischemia followed by 90 min of reperfusion. During ischemia, propofol (12 µg/mL in saline) was perfused through the aorta at 60 µL/min. We found that application of high-concentration propofol during ischemia combined with low-concentration propofol (1.2 µg/mL) administered before ischemia and during reperfusion significantly improved postischemic myocardial functional recovery without depressing cardiac mechanics before ischemia, as is seen when high-concentration propofol was applied prior to ischemia and during reperfusion. The functional enhancement is associated with increased heart tissue antioxidant capacity and reduced lipid peroxidation. We conclude that high-concentration propofol application during ischemia could be a potential therapeutic and anesthetic strategy for patients with preexisting myocardial dysfunction.Key words: propofol, ischemia, heart, rat, oxidative stress.

Cyclic AMP is involved in cardioregulation by multiple neuropeptides encoded on the FMRFamide gene

1999 ◽  
Vol 202 (19) ◽  
pp. 2595-2607 ◽  
Author(s):  
D. Willoughby ◽  
M.S. Yeoman ◽  
P.R. Benjamin
Keyword(s):  
Cyclic Amp ◽  
Lymnaea Stagnalis ◽  
Isolated Heart ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Heart Tissue ◽  
Heart Beat ◽  
Guanosine Monophosphate ◽  
Force Of Contraction

We have used a combination of biochemical and pharmacological techniques to investigate the role of the cyclic nucleotides, 3′, 5′-cyclic adenosine monophosphate (cyclic AMP) and 3′,5′-cyclic guanosine monophosphate (cyclic GMP), in mediating the cardioregulatory effects of FMRFamide and other neuropeptides encoded on exon II of the FMRFamide gene of Lymnaea stagnalis. The ‘isoleucine’ peptides (EFLRIamide and pQFYRIamide) produced complex biphasic effects on the frequency, force of contraction and tonus of the isolated heart of L. stagnalis, which were dependent on adenylate cyclase (AC) activity of the heart tissue. At a control rate of cyclic AMP production of less than or equal to 10 pmoles min(−)(1)mg(−)(1) protein, the ‘isoleucine’ peptides produced a significant increase in AC activity in heart membrane preparations. This suggested that the enhanced AC activity is responsible for the stimulatory effects of the ‘isoleucine’ peptides on frequency and force of contraction of heart beat. This excitation sometimes followed an initial ‘inhibitory phase’ where the frequency of beat, force of contraction and tonus of the heart were reduced by the ‘isoleucine’ peptides. Hearts that showed the inhibitory phase of the ‘isoleucine’ response, but characteristically lacked the delayed excitatory phase, were found to have high levels of membrane AC activity (breve)10 pmoles min(−)(1)mg(−)(1) protein in controls. Application of the ‘isoleucine’ peptides to membrane homogenate preparation from these hearts failed to increase AC activity. The addition of FMRFamide produced significant increases in the rate of cyclic AMP production in the heart membrane preparations, which could account, at least in part, for the cardioexcitatory effects of this peptide in the isolated whole heart. A membrane-permeable cyclic AMP analogue (8-bromo-cyclic AMP) and an AC activator (forskolin) were also cardioexcitatory. The peptide SEEPLY had no effects on the beat properties of the isolated heart and did not alter AC activity. The activity of the membrane-bound (particulate) guanylate cyclase (GC) was not significantly affected by any of the peptides.

Membranotropic activity of taurine derivatives

2020 ◽  
Author(s):  
Petr D. Shabanov ◽  
Ludmila K. Khnychenko
Keyword(s):  
Sulfonic Acid ◽  
Lymnaea Stagnalis ◽  
Calcium Influx ◽  
Ionic Currents ◽  
Isolated Neurons ◽  
Excitable Cells ◽  
Potassium Efflux ◽  
Low Concentrations ◽  
High Concentrations ◽  
Derivatives Of

The aim of the work. To evaluate the effect of n-phenylalkyl derivatives of taurine on changes in transmembrane ion currents of potential-controlled ion channels of isolated neurons. Materials and methods. The method of intracellular dialysis and fixation of membrane potential on isolated neurons of the great pond truncatula (Lymnaea stagnalis) and hornbill (Planorbarius corneus) was used. The n-phenylalkyl derivatives of taurine (1-phenyl-2-isopropylaminoethanesulfonic acid; benzylaminoethane sulfonic acid isopropylamide; phenethylaminoethane sulfonic acid isopropylamide) or the comparison drug taurine was dissolved in external solutions and studied at concentrations of 1, 10, 100 and 1000 M. Results. The results demonstrate that n-phenilalkyl derivatives of taurine in low concentrations (1; 10 M) have a modulating effect on electrically excitable cells, and in high concentrations (100; 1000 M) reduce the sodium-calcium influx and potassium efflux ionic currents, have a channel blocking effect. Conclusion. N-phenylalkyl derivatives of taurine reduces the excitability of cells contribute to the suppression of synaptic potentials, ion gradients of the cells.

Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

1992 ◽  
Vol 68 (05) ◽  
pp. 570-576 ◽  
Author(s):  
Mary A Selak
Keyword(s):  
Neutrophil Elastase ◽  
Cell Activation ◽  
Thromboxane A2 ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Low Concentrations ◽  
High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

Aggregation of Cat Platelets in Vitro

1970 ◽  
Vol 23 (03) ◽  
pp. 601-620 ◽  
Author(s):  
Th. B Tschopp
Keyword(s):  
Adenosine Monophosphate ◽  
Blood Collection ◽  
Base Line ◽  
Reversible Aggregation ◽  
Low Concentrations ◽  
Irreversible Aggregation ◽  
High Concentrations ◽  
Two Phases ◽  
Improved Technique

SummaryAggregation of cat platelets in the citrated plasma is examined by means of Born’s absorptiometer. A marked tendency of the platelets of this species to spontaneous aggregation necessitated first of all the development of an improved technique of blood collection.A hypothesis according to which 5-HT is released from the platelets, explains the absence of oscillations on the base line of the absorptiometer, the absence of platelet swelling, when ADP is added, and the effect of stirring on the aggregation curves in cat PRP. The average volume of cat platelets amounts to 10.46 μ3 when directly fixed in the blood, when fixed from PRP to 12.17 μ3, when fixed from stirred PRP to 13.51 μ3.In low concentrations (0.3-2 μM) ADP produce reversible aggregation; in narrowly restricted, individually dissimilar mean concentrations irreversible aggregation in two phases and in high concentrations, irreversible aggregation in one phase. Like ADP serotonin produces 2 phase irreversible aggregation in concentrations of 3-10 μM, but unlike ADP, the aggregation velocity decreases again with high 5-HT concentrations (>100 μM). Adrenaline does not produce aggregation and it is likely that adenosine and adenosine monophosphate inhibit the aggregation by serotonin but not by ADP. Species differences in the aggregation of human, rabbit and cat platelets are discussed.

The Action of an Aniline Derivative (AN 162) on Blood Coagulation and on Platelets

1971 ◽  
Vol 26 (01) ◽  
pp. 145-166
Author(s):  
E Deutsch ◽  
K Lechner ◽  
K Moser ◽  
L Stockinger
Keyword(s):  
Blood Coagulation ◽  
Citric Acid Cycle ◽  
Second Phase ◽  
Aniline Derivative ◽  
Acid Cycle ◽  
Enhancing Effect ◽  
Low Concentrations ◽  
Dual Action ◽  
High Concentrations ◽  
Induced Aggregation

Summary1. The aniline derivative AN 162, Donau Pharmazie, Linz, Austria, has a dual action on the blood coagulation: an anticoagulant and an coagulation enhancing effect.2. The anticoagulant action may only be demonstrated with high concentrations (over 1 X 10”3 M related to plasma) preferentially in PPP. It is partially caused by an inhibition of the endogenous way of generation of the prothrombin converting principle. In addition it is suggested that it interferes with the fibrinogen-fibrin reaction in a manner not yet understood.3. The coagulant action is caused by a greater availability of platelet constituents at low concentrations of AN 162 (over 1 × 10-4 M) and by the induction of a release reaction at higher concentrations. The platelet factors 3 and 4, serotonin, adenine, and acid phosphatase are released.4. AN 162 inhibits platelet aggregation. This inhibition can be demonstrated by the PAT of Breddin and in the stirred aggregation test of Born. It is more effective to inhibit the collagen-induced and the second phase of the adrenaline-induced aggregation than the ADP induced one. The platelet retention (test of Hellem) is also reduced.5. The action of AN 162 on the platelets is caused by a damage of the platelet membrane which becomes permeabel for both, soluble platelet constitutents and granula.6. AN 162 interferes with the energy metabolism of the platelets. It causes a loss of ATP, and inhibits the key-enzymes of glycolysis, citric acid cycle, fatty acid oxydation and glutathione reduction.7. AN 162 inhibits the growth of fibroblasts without influence on mitosis.

Functional Involvement of Thrombospondin in Platelet Aggregation Induced by Low Versus High Concentrations of Thrombin

1986 ◽  
Vol 55 (01) ◽  
pp. 136-142 ◽  
Author(s):  
K J Kao ◽  
David M Shaut ◽  
Paul A Klein
Keyword(s):  
Platelet Aggregation ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Activated Platelets ◽  
Low Concentrations ◽  
Platelet Binding ◽  
Functional Involvement ◽  
Thrombin Activation ◽  
Platelet Aggregates ◽  
High Concentrations

SummaryThrombospondin (TSP) is a major platelet secretory glycoprotein. Earlier studies of various investigators demonstrated that TSP is the endogenous platelet lectin and is responsible for the hemagglutinating activity expressed on formaldehyde-fixed thrombin-treated platelets. The direct effect of highly purified TSP on thrombin-induced platelet aggregation was studied. It was observed that aggregation of gel-filtered platelets induced by low concentrations of thrombin (≤0.05 U/ml) was progressively inhibited by increasing concentrations of exogenous TSP (≥60 μg/ml). However, inhibition of platelet aggregation by TSP was not observed when higher than 0.1 U/ml thrombin was used to activate platelets. To exclude the possibility that TSP inhibits platelet aggregation by affecting thrombin activation of platelets, three different approaches were utilized. First, by using a chromogenic substrate assay it was shown that TSP does not inhibit the proteolytic activity of thrombin. Second, thromboxane B2 synthesis by thrombin-stimulated platelets was not affected by exogenous TSP. Finally, electron microscopy of thrombin-induced platelet aggregates showed that platelets were activated by thrombin regardless of the presence or absence of exogenous TSP. The results indicate that high concentrations of exogenous TSP (≥60 μg/ml) directly interfere with interplatelet recognition among thrombin-activated platelets. This inhibitory effect of TSP can be neutralized by anti-TSP Fab. In addition, anti-TSP Fab directly inhibits platelet aggregation induced by a low (0.02 U/ml) but not by a high (0.1 U/ml) concentration of thrombin. In conclusion, our findings demonstrate that TSP is functionally important for platelet aggregation induced by low (≤0.05 U/ml) but not high (≥0.1 U/ml) concentrations of thrombin. High concentrations of exogenous TSP may univalently saturate all its platelet binding sites consequently interfering with TSP-crosslinking of thrombin-activated platelets.

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