The effect of theophylline on amine-induced cardiac cyclic AMP and cardiac contractile force

1977 ◽  
Vol 55 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Terry T. Martinez ◽  
John H. McNeill
Keyword(s):  
Cyclic Amp ◽  
Dose Response ◽  
Calcium Metabolism ◽  
Response Curve ◽  
Contractile Force ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Rat Atria ◽  
Contractile Effect ◽  
Cardiac Contractile

In the isolated electrically driven rat atria, theophylline (5 × 10−4 M) produced a small but significant increase in cyclic AMP content which was prevented by reserpine pretreatment. Theophylline was also found to exert a direct contractile effect, unrelated to cyclic AMP, in atria obtained from reserpine-pretreated animals. The norepinephrine inotropic response was attenuated after 3 min, enhanced after 15 min, and abolished after 60 min of exposure to theophylline (5 × 10−4 M). The maximum phenylephrine inotropic response was not significantly changed after 15 min of exposure to theophylline; however, there was a slight shift to the left of the phenylephrine dose–response curve. The effect of theophylline on cyclic AMP appeared to be additive with the norepinephrine and phenylephrine responses. The effect of theophylline on amine-induced cardiac cyclic AMP and contractile force showed no correlation between the contractile and the cyclic AMP effects at the different times tested. It is concluded that the inotropic effects of theophylline in rat atria are not mediated through cyclic AMP; instead, the methylxanthines may exert their effects on the heart through changes in calcium metabolism.

scholarly journals Histamine H2 receptors on foetal-bovine articular chondrocytes

1983 ◽  
Vol 212 (2) ◽  
pp. 517-520 ◽  
Author(s):  
D J Taylor ◽  
J R Yoffe ◽  
D E Woolley
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Dose Response ◽  
Response Curve ◽  
Articular Chondrocytes ◽  
Monolayer Cultures ◽  
H2 Receptors ◽  
Bovine Articular Chondrocytes ◽  
The Right ◽  
H1 Antagonists

The dose-response curve of histamine-induced cyclic AMP elevation in monolayer cultures of primary foetal-bovine articular chondrocytes was displaced to the right by cimetidine. In addition, H2 but not H1 antagonists prevented the histamine-induced cyclic AMP elevation, suggesting histamine activates chondrocyte adenylate cyclase through an H2 receptor.

scholarly journals Inhibition by somatostatin of amylase secretion induced by calcium and cyclic AMP in rat pancreatic acini

1994 ◽  
Vol 304 (2) ◽  
pp. 531-536 ◽  
Author(s):  
H Ohnishi ◽  
T Mine ◽  
I Kojima
Keyword(s):  
Cyclic Amp ◽  
G Protein ◽  
Pertussis Toxin ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Amylase Secretion ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Pancreatic Acini

It has recently been shown that somatostatin inhibits amylase secretion from isolated pancreatic acini by reducing cyclic AMP (cAMP) production [Matsushita, Okabayashi, Hasegawa, Koide, Kido, Okutani, Sugimoto and Kasuga (1993) Gastroenterology 104, 1146-1152]. To date, however, little is known as to the other mechanism(s) by which somatostatin inhibits amylase secretion in exocrine pancreas. To investigate the action of somatostatin independent of cAMP generation, we examined the effect of somatostatin in isolated rat pancreatic acini stimulated by 1 microM calcium ionophore A23187 and 1 mM 8-bromo-cyclic AMP (8Br-cAMP). Somatostatin inhibited amylase secretion evoked by a combination of A23187 and 8Br-cAMP in a dose-dependent manner. The maximum inhibition was obtained by 10(-7) M somatostatin, and at this concentration somatostatin inhibited the effect of A23187 and 8Br-cAMP by approximately 30%. In electrically permeabilized acini, an elevation of free calcium concentration resulted in an increase in amylase secretion and cAMP enhanced the secretion evoked by calcium. cAMP shifted the dose-response curve for calcium-induced secretion leftwards and elevated the peak value of secretion. Somatostatin inhibited the effect of cAMP on calcium-induced amylase secretion by shifting the dose-response curve to the right. To determine the involvement of a G-protein(s), we examined the effect of somatostatin in acini pretreated with pertussis toxin. Pretreatment of acini with pertussis toxin completely blocked somatostatin-inhibition of amylase-secretion evoked by A23187 and 8Br-cAMP. These results indicate that somatostatin decreases amylase secretion induced by cAMP and calcium by reducing the calcium sensitivity of exocytosis. A pertussis toxin-sensitive G-protein is also involved in this step.

Pyruvate potentiates inotropic effects of isoproterenol and Ca2+ in rabbit cardiac muscle preparations

2000 ◽  
Vol 279 (2) ◽  
pp. H702-H708 ◽  
Author(s):  
Hans-Peter Hermann ◽  
Oliver Zeitz ◽  
Boris Keweloh ◽  
Gerd Hasenfuss ◽  
Paul M. L. Janssen
Keyword(s):  
Energy Demand ◽  
Contractile Force ◽  
Potential Importance ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Individual Effects ◽  
Positive Inotropic Effects ◽  
Series Of Experiments ◽  
The Individual ◽  
Mere Addition

Catecholamines and elevated extracellular Ca2+concentration ([Ca2+]o) augment contractile force by increased Ca2+ influx and subsequent increased sarcoplasmic reticulum (SR) Ca2+ release. We tested the hypothesis that pyruvate potentiates Ca2+ release and inotropic response to isoproterenol and elevated [Ca2+]o, since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca2+]o of 1.25 mM, pyruvate (10 mM) alone increased developed force (Fdev) from 1.89 ± 0.42 to 3.62 ± 0.62 (SE) mN/mm2 ( n = 8, P < 0.05) and isoproterenol (10−6 M) alone increased Fdev from 2.06 ± 0.55 to 25.11 ± 2.1 mN/mm2 ( P < 0.05), whereas the combination of isoproterenol and pyruvate increased Fdevoverproportionally from 1.89 ± 0.42 to 33.31 ± 3.18 mN/mm2 ( P < 0.05). In a separate series of experiments, we assessed SR Ca2+ content by means of rapid cooling contractures and observed that, despite no further increase in Fdev by increasing [Ca2+]o from 8 to 16 mM, 10 mM pyruvate could still increase Fdev from 26.4 ± 6.8 to 29.7 ± 7.1 mN/mm2( P < 0.05, n = 9) as well as the Ca2+ load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca2+, because in the presence of pyruvate, Ca2+ and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects.

Ontogeny of positive inotropic responses to sympathomimetic agents and of myocardial adrenoceptors in rats

1994 ◽  
Vol 72 (4) ◽  
pp. 361-367 ◽  
Author(s):  
Arjumand Inayatulla ◽  
Ding-You Li ◽  
Sylvain Chemtob ◽  
Daya R. Varma
Keyword(s):  
Contractile Force ◽  
Inotropic Response ◽  
Chemical Sympathectomy ◽  
Adult Rats ◽  
Maximal Increase ◽  
Inotropic Effects ◽  
Mediated Effects ◽  
Adrenoceptor Agonist ◽  
6 Hydroxydopamine ◽  
Inotropic Responses

Positive inotropic efficacies (maximal increase in contractile force) and potencies of the α-adrenoceptor agonist methoxamine and β-adrenoceptor agonist isoprenaline were determined on electrically driven (1 Hz) ventricular strips from rats aged 0.5, 1, 2, 3, 6, and 10 (adult) weeks. The inotropic response to methoxamine significantly decreased after 2 weeks of age. The inotropic potency of isoprenaline was slightly but significantly lower at all ages than at 0.5 weeks of age. Up to 2 weeks of age, the maximal inotropic effect of methoxamine was comparable with that of isoprenaline, thereafter it was but markedly less. Phenylephrine behaved like methoxamine, and noradrenaline like isoprenaline. The effect of methoxamine was antagonized by prazosin but not by propranolol; the reverse was true for isoprenaline. Injections at birth of triiodothyronine and dexamethasone exerted minimal effects on the inotropic responses to methoxamine and isoprenaline. Chemical sympathectomy with 6-hydroxydopamine caused supersensitivity to the inotropic effects of isoprenaline but produced subsensitivity to responses to methoxamine at 1 week; effects of methoxamine at 3 and 6 weeks of age were not altered by sympathectomy. No significant differences in α1 or β1-adrenoceptor densities or affinities in ventricular membranes from 7-day-old and adult rats were found. It is concluded that the positive inotropic responses to sympathomimetic amines decline with age, the decline is most marked in the case of α1-adrenoreceptor-mediated effects, and these changes do not appear to be due to a decrease in the number or affinity of α1- and β1-adrenoceptors.Key words: myocardial adrenocepters, methoxamine, isoprenaline, phenylephrine, noradrenaline, ontogeny, inotropic responses.

CONTRACTION OF THE RABBIT MAMMARY STRIP IN VITRO IN RESPONSE TO OXYTOCIN

1965 ◽  
Vol 48 (2) ◽  
pp. 186-198 ◽  
Author(s):  
Richard D. Moore ◽  
M. X. Zarrow
Keyword(s):  
Mechanism Of Action ◽  
Dose Response ◽  
Response Curve ◽  
Contractile Response ◽  
Post Partum ◽  
Mammary Glands ◽  
Contractile Force ◽  
Maximum Response ◽  
Force Of Contraction

ABSTRACT The isometric contractile response to oxytocin has been studied in vitro utilizing strips of tissue from rabbit mammary glands. Responses were maximal at resting tensions of 200–400 mg/mm2. The force of contraction increased from the beginning of lactation to about 9 days post partum and then leveled off. Little or no response is noted below 15° C and the maximum response is obtained in the range of 32 to36°C. Irreversible changes begin above 41° C. As little as 0.1 mU oxytocin/ml could be detected and the dose-response curve was demonstrated statistically to be linear between the dosages of 0.5 to 10 mU oxytocin/ml. The doseresponse curve reached a plateau at about 8–11 mU/ml. Replacing sodium with potassium resulted in a logarithmic decrease of contractile force with time. This decrease was partially reversible. The strip became inexcitable in calcium free Tyrode's solution. Excitability was again established by adding calcium. Other than to oxytocin, the mammary strip responded only to acetylcholine. The effect of acetylcholine could be blocked by atropine and this treatment did not affect the response to oxytocin. The site and mechanism of action of oxytocin are discussed.

scholarly journals The involvement of protein phosphorylation in stimulus-secretion coupling in the mouse exocrine pancreas

1983 ◽  
Vol 210 (2) ◽  
pp. 353-359 ◽  
Author(s):  
M L Roberts ◽  
F R Butcher
Keyword(s):  
Cyclic Amp ◽  
Protein Phosphorylation ◽  
Dose Response ◽  
Exocrine Pancreas ◽  
Response Curve ◽  
Dose Response Curve ◽  
Amylase Secretion ◽  
Ionophore A23187 ◽  
Muscarinic Agonist ◽  
Derivatives Of

Secretagogue-induced protein phosphorylation was studied in the mouse pancreas in vitro, by using polyacrylamide-gel electrophoresis to separate the labelled proteins. Muscarinic cholinergic agonists increased the phosphorylation of a single band, which corresponded to Mr 32000, when the tissue was incubated with Ca2+ present in the extracellular medium, but not in Ca2+-free Krebs solution. In the presence of Ca2+, ionophore A23187 stimulated phosphorylation of the same band. The dose-response curve for carbachol-induced phosphorylation was biphasic, with maximum response at 1.0 microM-carbachol, and lesser responses when greater concentrations were used. This resembles the dose-response curve for carbachol-induced amylase secretion. The data suggest that the muscarinic-agonist-induced protein phosphorylation is stimulated secondarily to elevation of cytosol [Ca2+] and do not support the idea that diacylglycerol formed from hydrolysis of phosphatidylinositol is the activator of the protein kinase. Derivatives of cyclic AMP stimulated phosphorylation of bands corresponding to Mr 95500, 32000 and 20000. The effects of dibutyryl cyclic AMP and bethanechol on the protein of Mr 32000 were not additive, suggesting that the two agents produced phosphorylation of the same site(s) on this protein. Since derivatives of cyclic AMP, which are not very effective secretagogues in the exocrine pancreas, stimulate phosphorylation of the protein of Mr 32000, it is difficult to argue that phosphorylation of this particular protein leads to protein secretion.

2-Chloroadenosine increases calcium mobilization from mouse calvaria in vitro

1982 ◽  
Vol 100 (2) ◽  
pp. 313-320 ◽  
Author(s):  
Ulf Lerner ◽  
Bertil B. Fredholm
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Bone Tissue ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Cyclic Amp Accumulation ◽  
Adenosine Analogue ◽  
Stimulation Of

Abstract. The effect of 2-chloroadenosine on bone resorption and on cyclic AMP formation in murine calvarial bones in vitro was investigated. 2-Chloroadenosine increased the release of 45Ca from the cultured bones, but had no effect on dead bones, indicating that the effect is cell mediated. The adenosine analogue remained in the medium for 48 h and caused a transient stimulation of the formation of cyclic AMP. The dose-response curve for the stimulatory effect on cyclic AMP accumulation was linear up to 10−4m. The dose-response curve for 45Ca release was linear from 3 × 10−7 m to 3 × 10−5 m but then showed a decline in the response. 8-Bromo cyclic AMP inhibited the release of 45Ca in 24 h cultures. The initial stimulatory effect on bone resorption by 2-chloroadenosine may therefore not depend on cyclic AMP. The level of inosine increased during culture indicating that adenosine is formed by bone tissue.

scholarly journals Effects of phorbol esters on α1-adrenergic-mediated and glucagon-mediated actions in isolated rat hepatocytes

1985 ◽  
Vol 228 (1) ◽  
pp. 277-280 ◽  
Author(s):  
J A García-Sáinz ◽  
F Mendlovic ◽  
M A Martínez-Olmedo
Keyword(s):  
Cyclic Amp ◽  
Dose Response ◽  
Response Curve ◽  
Phorbol Esters ◽  
Rat Hepatocytes ◽  
Metabolic Effects ◽  
Isolated Rat Hepatocytes ◽  
The Right ◽  
Isolated Rat ◽  
Stimulation Of

Phorbol 12-myristate 13-acetate (PMA) inhibited the stimulation of ureogenesis produced by adrenaline, but produced a minimal displacement to the right of the dose-response curve for glucagon. However, PMA diminished the accumulation of cyclic AMP induced by glucagon. Dissociation between the cyclic AMP concentrations and the metabolic effects induced by glucagon is evidenced in the presence of phorbol esters.

Effects of peptide leukotrienes on cardiac dynamics in rat, cat, and guinea pig hearts

1985 ◽  
Vol 249 (3) ◽  
pp. H477-H484 ◽  
Author(s):  
D. M. Roth ◽  
D. J. Lefer ◽  
C. E. Hock ◽  
A. M. Lefer
Keyword(s):  
Guinea Pig ◽  
Coronary Perfusion Pressure ◽  
Contractile Force ◽  
Coronary Perfusion ◽  
Papillary Muscles ◽  
Inotropic Effects ◽  
Isolated Hearts ◽  
Cardiac Contractile ◽  
Myocardial Contractile Force ◽  
Leukotriene Antagonist

The purpose of the present investigation was to examine potential inotropic effects of leukotrienes C4 (LTC4) and D4 (LTD4) in relation to their potent coronary constricting effects. The experiments were carried out in isolated Langendorff perfused hearts and isolated electrically driven isometrically contracting papillary muscle preparations. Tissues from cat, rat, and guinea pig were used in the study. Both LTC4 and LTD4 at 50 ng/ml had no effect on papillary muscles isolated from the rat, guinea pig, or cat. These papillary muscles responded to known negative inotropic agents including pentobarbital sodium and methanol. In isolated hearts perfused under constant flow, both LTC4 and LTD4 at 50 ng/ml increased coronary perfusion pressure and decreased contractile force of the heart in all three species. In hearts perfused under constant pressure perfusion, both LTC4 and LTD4 decreased coronary flow with concomitant decreases in contractile force. The leukotriene antagonist, FPL 55712, blocked both the coronary constrictor and the cardiodepressant effects of both leukotrienes. Pentobarbital (100 micrograms/ml) significantly decreased cardiac contractile force without inducing coronary vasoconstriction. These findings demonstrate that LTC4 and LTD4 do not possess direct negative inotropic activity in cardiac muscles of these three species. However, LTC4 and LTD4 are potent coronary constrictors that can secondarily decrease myocardial contractile force via their coronary constrictor action.

Arteriolar responses to norepinephrine and ouabain in early 1-kidney, 1-clip hypertension in rats

1985 ◽  
Vol 249 (4) ◽  
pp. H851-H858
Author(s):  
H. W. Overbeck
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Response Curves ◽  
Sodium Potassium ◽  
Inotropic Effects ◽  
Arteriolar Wall ◽  
Vascular Beds ◽  
Normotensive Control

We assessed the role of putative circulating ouabainlike factors on in vivo arteriolar function in rats with very early (less than or equal to 7 days, mean 3 days), benign, one-kidney, one-clip (1K1C) hypertension. Thus we measured vascular responses in vasodilated (nitroprusside or adenosine), vascularly isolated, innervated hindlimb vascular beds of chloralose-anesthetized 1K1C rats perfused with their own blood at 1 ml/min. Complete dose-response curves to norepinephrine in 19 1K1C compared with 25 uninephrectomized (1K) normotensive control rats showed unchanged thresholds and 50% effective dosages. Magnitude of ouabain-induced leftward shifts of the dose-response curve in 29 1K1C and 30 1K rats were similar. In 1K1C, compared with 1K, limb resting resistance was elevated by 45% (P less than 0.001), and limb resistance at maximal vasodilation was elevated by 15% (P less than 0.02). These results provide no evidence in this form and stage of hypertension that humoral ouabainlike inhibitors of the sodium-potassium pump evoke physiologically significant inotropic effects in arterioles in vivo. However, the results suggest that significant increases in arteriolar wall-to-lumen ratio occur in the earliest stages (3 days) of hypertension and probably contribute to the elevated resistance.

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