Potentiation of Adenosine and the Adenine Nucleotides by Dipyridamole

Stafford, Anne

doi:10.1111/j.1476-5381.1966.tb01888.x

Cited by 130 publications

(56 citation statements)

References 15 publications

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“…It Afonso, 1970;Sattin & Rall, 1970;Osswald, 1975;Ally & Nakatsu, 1976;Sawynok & Jhamandas, 1976;Okwuasaba et al, 1977). In contrast, dipyridamole and hexobendine have been shown to potentiate the inhibitory effect of adenosine and adenine nucleotide in the heart, intestine and trachea (Stafford, 1966;Kolassa, Pfleger & Rummel, 1970; At arrow, theophylline 30 gM was added to the superfusion solution. Satchell et al, 1972;Coleman, 1976).…”

Section: Discussionmentioning

confidence: 99%

The Development of Tachyphylaxis to Electrical Stimulation in Guinea‐pig Ileal Longitudinal Muscles and the Possible Participation of Adenosine and Adenine Nucleotides

Hayashi

Kunitomo

Mori

et al. 1978

British J Pharmacology

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Electrically (30 Hz) induced contractions of guinea‐pig isolated ileal longitudinal muscles were reduced by tetrodotoxin (1 μm), atropine (1 μm), adenosine (30 μm) and morphine (10 μm). When stimulated with 10 or 30 Hz for 10 s at 1 min intervals, a progressive decline of amplitude of the contraction was seen (development of tachyphylaxis). At this time, the contractile response to 1,1‐dimethyl‐4‐phenylpiperazinium iodide (DMPP) (10 μm) was also greatly reduced. The smaller responses to electrical stimulation and DMPP during tachyphylaxis were restored to their initial amplitude by the addition of theophylline (10 μm). The appearance of tachyphylaxis was prevented by pretreatment with theophylline (1 to 10 μm) and was greatly accelerated by pretreat‐ment with dipyridamole (0.1, 1 μm). In [14C]‐choline or [3H]‐adenosine preloaded muscle strips, electrical stimulation (30 Hz) increased the 14C‐ or 3H‐output, the effect being sensitive to tetrodotoxin blockade. The tachyphylaxis to electrical stimulation was accompanied by a considerable and sustained increase in 3H‐output, an effect that was accelerated by dipyridamole (1 μm). The 14C‐output initially increased but fell off gradually with the development of tachyphylaxis at which time theophylline (30 1) reversed the fall. There was a marked increase in the proportion of released [3H]‐adenosine to its derivatives during the development of tachyphylaxis. Approximately 60% of the released total radioactivity after tachyphylaxis was found to be [3H]‐adenosine. These results suggest that the development of tachyphylaxis may be closely associated with the release of endogenous adenosine derivatives (mostly adenosine) which have presynaptic inhibitory actions on the cholinergic elements in guinea‐pig ileum.

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Section: Discussionmentioning

confidence: 99%

The Development of Tachyphylaxis to Electrical Stimulation in Guinea‐pig Ileal Longitudinal Muscles and the Possible Participation of Adenosine and Adenine Nucleotides

Hayashi

Kunitomo

Mori

et al. 1978

British J Pharmacology

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“…This dose was repeated at 2 min intervals for the duration of the experiment (2-3 h). When injected at 20-40 min intervals, all the pyrimido-pyrimidine and pteridine derivatives prolonged the period of heart block produced by adenosine as described for dipyridamole by Stafford (1966). In each of the first eight experiments several of the potenitiating compounds were injected in succession in order to obtain a rough estimate of their relative potency.…”

Section: Resultsmentioning

confidence: 99%

“…Adenosine potentiation Adenosine produces a transient period of heart block in the guinea-pig, and this response was chosen as suitable for studying the degree of adenosine potentiation by pyrimidopyrimidines and pteridines because dipyridamole by itself does not produce it (Stafford, 1966).…”

Section: Methodsmentioning

confidence: 99%

“…This compound has been shown to potentiate adenosine in its actions on several tissues (Scholtholt, Bussman & Lochner, 1965 ;Stafford, 1966) and it has been suggested that some of its effects, including dilatation of the coronary vessels, may arise indirectly through potentiation of endogenous adenosine (West, Bellet, Manzoli & Muller, 1962;Gerlach & Deuticke, 1963;Stafford, 1966).…”

Section: Introductionmentioning

confidence: 99%

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The possible role of adenosine in the coronary dilator action of some pyrimidopyrimidines and pteridines

Nott

1970

British J Pharmacology

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Summay1. The abilities of some pyrimidopyrimidines (including dipyridamole) and pteridine derivatives to potentiate heart block produced by adenosine in the guinea-pig and to produce coronary dilatation in kitten hearts were investigated. 2. The results demonstrated a correlation between adenosine potentiating and coronary dilating activities of the compounds studied, and are therefore compatible with the concept that compounds of the dipyridamole type owe their coronary dilator activity to potentiation of endogenous adenosine. IntroductionDipyridamole (2,6 -bis(diethanolamino) -4,8 -dipiperidino -pyrimido(5,4 -d)pyrimidine) is a coronary dilator drug introduced for the treatment of angina (Charlier,

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“…In the 1980s, several investigators reexamined the electrophysiologic effects of adenosine. 2,3) Belardinelli, et al showed that adenosine produced various degrees of dose-related reversible AV block in guinea pig and rabbits hearts perfused by the Langendorff technique, and the negative dromotropic effects were localized to AV nodal tissue. 3,4) Of interest was the finding that when AV nodal conduction was impaired by an intervention such as hypoxia or ischemia, which caused increased release of adenosine from myocardial cells, the AV conduction delay and block were similar to those caused by exogenous adenosine.…”

Section: T He Electrophysiologic Effects Of Adenosine (Ado) Andmentioning

confidence: 99%

Effects of the Antianginal Drug Trapidil on Atrioventricular Conduction Disturbances During Acute Myocardial Ischemia

et al. 2012

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SummaryAdenosine and related compounds have been shown to produce atrioventricular (AV) conduction block during acute myocardial ischemia. We investigated the effects of the antianginal drug trapidil, which has been shown to inhibit phosphodiesterase, on AV conduction disturbances in a canine model of acute myocardial ischemia. In 35 anesthetized dogs, the AV node artery was cannulated and perfused with arterial blood. Adenosine (300 μg, 650 μg, or 1000 μg) was injected into the AV node artery. With administration of adenosine at 300 μg, 650 μg, or 1000 μg, the atrio-His (AH) interval was increased by 14.6 ms, 22.3 ms, and 29.7 ms, respectively. The effects of adenosine were potentiated by pretreatment with intravenous dipyridamole (250 μg/kg), an inhibitor of adenosine uptake, but the effects of adenosine were attenuated with intravenous trapidil (3 mg/kg), an inhibitor of phosphodiesterase. AV node artery occlusion resulted in prolongation of the AH interval in 4 of 12 dogs. The ischemia-induced AH prolongation was potentiated with intravenous dipyridamole and attenuated with intravenous trapidil. AV conduction disturbances associated with inferior myocardial infarction may be related in part to endogenously released adenosine, and trapidil may be useful in treating AV block associated with acute AV node ischemia. (Int Heart J 2012; 53: 187-192) Key words: Atrioventricular block, Acute myocardial ischemia, Adenosine, Dipyridamole, Trapidil T he electrophysiologic effects of adenosine (ADO) and other adenine derivatives were first described by Drury and Szent-Gyorgi in 1929, 1) who clearly demonstrated that intravenous administration of adenosine produced a decrease in sinus rate and transient atrioventricular (AV) block. Adenosine was found to be a mediator of many physiologic phenomena, and most of the interest in its effects on the cardiovascular system were centered on its ability to regulate regional blood flow in the heart and other organs. In the 1980s, several investigators reexamined the electrophysiologic effects of adenosine.2,3) Belardinelli, et al showed that adenosine produced various degrees of dose-related reversible AV block in guinea pig and rabbits hearts perfused by the Langendorff technique, and the negative dromotropic effects were localized to AV nodal tissue.3,4) Of interest was the finding that when AV nodal conduction was impaired by an intervention such as hypoxia or ischemia, which caused increased release of adenosine from myocardial cells, the AV conduction delay and block were similar to those caused by exogenous adenosine. 4,5) Hypoxia in isolated perfused mammalian heart 4) or ischemia of the AV node (by ligation of the AV node artery) in canine heart in situ 6) caused prolongation of the AH interval that often resulted in second-degree AV block. The fact that the hypoxia-or ischemia-induced AV conduction block could be modified in a predictable manner by interventions known to antagonize and/ or potentiate the actions of adenosine lends support to the concept that the dromot...

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Potentiation of Adenosine and the Adenine Nucleotides by Dipyridamole

Cited by 130 publications

References 15 publications

The Development of Tachyphylaxis to Electrical Stimulation in Guinea‐pig Ileal Longitudinal Muscles and the Possible Participation of Adenosine and Adenine Nucleotides

The Development of Tachyphylaxis to Electrical Stimulation in Guinea‐pig Ileal Longitudinal Muscles and the Possible Participation of Adenosine and Adenine Nucleotides

The possible role of adenosine in the coronary dilator action of some pyrimidopyrimidines and pteridines

Effects of the Antianginal Drug Trapidil on Atrioventricular Conduction Disturbances During Acute Myocardial Ischemia

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