The release of substances like acetylcholine and adrenaline by the isolated rabbit heart

Day, Margaret

doi:10.1113/jphysiol.1956.sp005665

Cited by 36 publications

(8 citation statements)

References 24 publications

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“…The evidence suggests that acetylcholine, of myogenic, not neurogenic, origin, is continuously formed in the myocardium (34)(35)(36)(37)(38). This locally formed acetylcholine is thought to be involved in the maintenance of muscle tone, motility, and rhythmicity, rather than in being involved in vagal control (35,38). The pacemaker is thought to be under the control of this locally formed acetylcholine (38).…”

Section: Significance Of Localizationmentioning

confidence: 99%

The Localization of Cholinesterase Activity in Rat Cardiac Muscle by Electron Microscopy

Karnovsky

1964

The Journal of Cell Biology

488

172

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A method has been developed for localizing sites of cholinesterase activity in rat cardiac muscle by electron microscopy. The method utilizes thiocholine esters as substrates, and is believed to be dependent on the reduction of ferricyanide to ferrocyanide by thiocholine released by enzymatic activity. The ferrocyanide thus formed is captured by copper to form fine, electron-opaque deposits of copper ferrocyanide, which sharply delineate sites of enzymatic activity at the ultrastructural level. Cholinesterase activity in formalin-fixed heart muscle was localized: (a) in longitudinal elements of the sarcoplasmic reticulum, but not in the T, or transverse, elements; and (b) in the A band, with virtually no activity noted in the M band, or in the H zone. The I band was also negative. No activity was detected in the sarcolemma, or in invaginations of the sarcolemma at the level of the Z band. The perinuclear element of the sarcoplasmic (endoplasmic) reticulum was frequently strongly positive. Activity at all sites was completely abolished by omitting the substrates, or by inhibition with eserine 10-4 M and diisopropylfluorophosphate 10-5 M. Eserine 10-5 M completely inhibited reaction in the sarcoplasmic reticulum, and virtually abolished that in the A band. These observations, together with the use of the relatively specific substrates and suitable controls to eliminate non-enzymatic staining, indicate that cholinesterase activity was being demonstrated. The activity in rat heart against different substrates was that of non-specific cholinesterases, in accordance with biochemical data. The activity in the A band was considered to be probably due to myosincholinesterase. It is proposed that the localization of cholinesterases in myocardium at the ultrastructural level should be taken into account in considering the possible functions of these myocardial enzymes, and it is hoped that knowledge of their localization will open up new avenues of approach in considering their physiological role in myocardium, which at present is not definitely known.

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Section: Significance Of Localizationmentioning

confidence: 99%

The Localization of Cholinesterase Activity in Rat Cardiac Muscle by Electron Microscopy

Karnovsky

1964

The Journal of Cell Biology

488

172

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“…Indeed indirect support for this concept arises from the observations that acetylcholine is known to be formed by certain non-nervous tissues (human placenta, Comline, 1947;Hebb & Ratkovic 1962: gill plates of Mytilu8 edulis, Bilbring, Burn & Shelley, 1953: spleen of horse and ox, Comline, 1947;Hebb, 1957). Certain experimental findings have also suggested the possibility of a non-nervous origin of acetylcholine in mammalian cardiac muscle (Briscoe & Burn, 1954;Day, 1956). This question became important in the course of studies on acetylcholine output by the intestine; it is also critical in the analysis of drug action where contractions of the guinea-pig ileum are involved.…”

Section: Introductionmentioning

confidence: 99%

The origin of acetylcholine released from guinea‐pig intestine and longitudinal muscle strips

Patón¹,

Zar²

1968

The Journal of Physiology

604

282

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SUMMMARY1. Strips of longitudinal muscle can be obtained from guinea-pig ileum either retaining or free from Auerbach's plexus.2. The denervated strip is unresponsive to electrical stimulation by brief shocks, whether given singly or in trains; it also fails to respond to nicotine or dimethylphenylpiperazinium iodide (DMPP), and eserine causes no spasm.3. Denervated strips neither contain detectable acetylcholine ( < 0 4 ng/ mg), nor release it spont&neously (< 5 pg/mg/min) or in response to stimulation (< 31 pg/mg/min). The acetylcholine metabolism of the innervated strip is therefore that of the adherent Auerbach's plexus. Innervated strips had a mean acetylcholine content of 28 ng/mg, a mean resting output of 94 pg/mg/min and an output in response to stimulation at 10 c/s of 700-1200 pg/mg/min.4. By comparing the responses of innervated and denervated strips it was concluded that arecoline, methylfurmethide, a,8l-ethylal-y-trimethylammonium propanediol iodide (2268 F), muscarine, histamine, tremorine, oxytocin, and substance P, like acetylcholine, act primarily on the smooth muscle directly; and that angiotensin, barium, potassium, m-bromophenyl choline ether and 5-hydroxytryptamine have a progressively increasing proportionate effect on the nerve plexus. Nicotine and DMPP were inactive in the absence of the plexus.5. The longitudinal muscle with its accompanying plexus contains about one quarter of the acetylcholine of the whole ileum, and is responsible for about one fifth of the output to electrical stimulation.6. The volley output of acetylcholine by the innervated strip declines sharply as rate of stimulation increases. Output of acetylcholine was reduced by morphine and by cocaine, particularly when resting or when stimulated at low rates.

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“…That the isolated rabbit ventricle can liberate acetylcholine during perfusion is evident from the experiments reported by Day (1956). When recirculated perfusion fluid from rabbit hearts, with and without the atria excised, was assayed on the frog heart and on the frog rectus, twothirds of the acetylcholine liberated was found to derive from the ventricles.…”

Section: Acetylcholine On Ventricular Pacemakersmentioning

confidence: 68%

A Depressant Effect of Acetylcholine on the Idio‐ventricular Pacemaker of the Isolated Perfused Rabbit Heart

Benforado

1958

British Journal of Pharmacology and Chemotherapy

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In Langendorff preparations of the isolated rabbit heart, excision of the atria and severance of the atrio-ventricular bundle resulted in the onset of idio-ventricular rhythm at a rate much below the original sino-atrial rate. The mean decrease in rate in twelve experiments was 61%. Acetylcholine perfusion decreased the idio-ventricular rate still further. Physostigmine augmented this effect while atropine prevented or abolished it. Similar results were obtained with a rat heart. The results indicate that a cholinergic receptor mechanism is present at pacemaker sites in mammalian ventricles. However, when rabbit ventricles, beating under atrio-ventricular nodal rhythm or idio-ventricular rhythm, were cooled to the point of cardiac arrest, acetylcholine failed to cause reappearance of the cardiac beat.Acetylcholine has been shown to affect the transmembrane atrial resting and action potentials in a number of species (Cranefield and Hoffman, 1958), and these effects present a basis for understanding the actions of this substance on rate, conduction velocity, and refractory period of atrial tissue. Effects on the transmembrane action potential of the frog ventricle have also been demonstrated, but experiments in which the effect of acetylcholine on the mammalian ventricular action potential was examined have proved negative (Brooks, Hoffman, Suckling, and Orias, 1955). Further, the generally accepted fact that the ventricle does not receive cholinergic innervation has been suggested as a reason for these negative results (Hoffman and Suckling, 1953;Brooks et al., 1955). The experiments presented here indicate that acetylcholine can decrease the idioventricular rate of the isolated perfused rabbit and rat heart, and that this effect is augmented by physostigmine and is reversed or prevented by atropine. The effect of acetylcholine on isolated rabbit ventricles cooled to the point of cardiac arrest was also examined. The results of 19 experiments are described. by McEwen (1956). The heart rate was measured from the electrocardiogram, which was recorded by leads from the two ventricles. In a few early experiments, heart rate was counted with the aid of a stopwatch by observing ventricular contractions on a kymograph drum. For the production of atrio-ventricular nodal rhythm the atria and interatrial septum were excised at the level of the atrio-ventricular groove. In the experiments on idio-ventricular rhythm, the atrio-ventricular bundle was severed by an additional cut in the inter-ventricular septum. Drugs employed were added to the bottles containing the perfusion fluid. Drug concentrations are expressed as g./l. of the base. When hearts were cooled, this was accomplished by the gradual adding of tap water and ice to the water-bath in which the perfusion coil was immersed. The rate of cooling was about 1/min. RESULTSIdio-ventricular Rhythm and the Effect of Acetylcholine Table I shows the change in rate produced in the isolated perfused rabbit heart by excision of the atria and severance of the atrio-ventricular b...

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The release of substances like acetylcholine and adrenaline by the isolated rabbit heart

Cited by 36 publications

References 24 publications

The Localization of Cholinesterase Activity in Rat Cardiac Muscle by Electron Microscopy

The Localization of Cholinesterase Activity in Rat Cardiac Muscle by Electron Microscopy

The origin of acetylcholine released from guinea‐pig intestine and longitudinal muscle strips

A Depressant Effect of Acetylcholine on the Idio‐ventricular Pacemaker of the Isolated Perfused Rabbit Heart

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