The Stimulating Effect of Acetylcholine on the Mammalian Heart and the Liberation of an Epinephrine-Like Substance by the Isolated Heart

Hoffmann, Francisco; Hoffmann, Elena J.; Middleton, Samuel; Talesnik, J

doi:10.1152/ajplegacy.1945.144.2.189

Cited by 140 publications

(40 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A stimulating action on the isolated rabbit or cat heart by ganglionic stimulants such as nicotine and ACh after atropine was described by Hoffmann, Hoffmann, Middleton and Talesnik (1945) and more recently on the isolated rabbit auricles by and Ginzel and Kottegoda (1953). The latter authors found that this effect could be blocked by HMI, and assumed the presence of peripheral sympathetic ganglia within the auricular tissue.…”

Section: Methodsmentioning

confidence: 93%

Some Aspects of the Pharmacology of an Homologous Series of Choline Esters of Fatty Acids

Schneider

Timms

Kyi

et al. 1957

British Journal of Pharmacology and Chemotherapy

View full text Add to dashboard Cite

The pharmacological effects of a series of fatty acid-choline esters have been studied on the isolated rabbit heart, the isolated guinea-pig ileum and the rat stomach. The effect changed with increasing chain length, and three different types of response were observed. The shortchain compounds produced depression of the isolated rabbit heart and spasm of the isolated guinea-pig ileum. Only one, butyrylcholine, had an erratic stimulating effect on hydrochloric acid secretion by the partially vagotomized rat stomach. Medium-chain compounds had a stimulating effect on the isolated rabbit heart, a mixed spasmogenic and relaxant effect on the isolated guinea-pig ileum, and no effect on the rat stomach. Long-chain compounds blocked the effect of acetylcholine on the isolated rabbit heart and the isolated guinea-pig ileum; they also depressed spontaneous hydrochloric acid secretion by the rat stomach. The nature of these three types of response is discussed.The present investigation is concerned with the pharmacology of the choline esters of an homologous series of saturated straight-chain monobasic fatty acids.Previous work was mainly concerned with the effect of these compounds on blood pressure. Hunt and Taveau (1911), in their extensive investigation of the pharmacology of a large number of choline derivatives, included the esters from acetylcholine (ACh) to pentanoylcholine and in addition palmitoylcholine, all of which occur in the series used in this work. They found that with increasing chain length the depressor effect declined, and a pressor effect was observed which in some cases became manifest after atropine but in others without atropine. These findings were confirmed and elaborated by le Heux (1921), Simonart (1932), Chang and Gaddum (1933, and Bovet and BovetNitti (1948). Fourneau and Page (1914) synthesized a series of these esters with even numbers of carbon atoms in the chain. Haemolytic action was most pronounced with the palmitic and stearic acid esters; it diminished with decreasing chain length, and was no longer found with members below dodecanoylcholine. In the present investigation an almost complete series of these esters was available. The effect of the chain length upon the pharmacological action was examined on the isolated mammalian heart, the motility of the small intestine, and the secretory response of the stomach. METHODSIsolated Rabbit Heart.-The usual Langendorff type of preparation with retrograde aortic perfusion was used. The composition of the perfusion solution used was: NaCl 9 g., KC1 0.42 g., CaCl2 0.24 g., NaHCO3 0.5 g., dextrose 1.0 g., distilled water 1 litre.The compounds tested were injected through the rubber-capped side-arm of the perfusion apparatus.Isolated Guinea-pig Ileum.-The ability of some of the compounds to induce spasm was expressed in terms of the concentration which caused an effect equal to that produced by 10'.5 M-ACh. This was determined upon the isolated guinea-pig ileum suspended in the 2.0 ml. bath of an automatic assay apparatus, similar to that desc...

show abstract

Section: Methodsmentioning

confidence: 93%

Some Aspects of the Pharmacology of an Homologous Series of Choline Esters of Fatty Acids

Schneider

Timms

Kyi

et al. 1957

British Journal of Pharmacology and Chemotherapy

View full text Add to dashboard Cite

show abstract

“…1). This latter increase was probably due to acetylcholineinduced release of endogenous norepinephrine which in turn increased cyclic AMP levels in the hearts (23).…”

Section: Effect Of Acetylcholine On Cyclic Nucleotide Levels and On Cmentioning

confidence: 97%

Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium.

Watanabe¹,

Besch²

1975

Circulation Research

229

View full text Add to dashboard Cite

The purpose of this study was to examine the mechanisms underlying adrenergiccholinergic antagonism in ventricular myocardium. Myocardial contractility, cyclic adenosine monophosphate (AMP) levels, and cyclic guanosine monophosphate (GMP) levels were measured in isolated guinea pig ventricles after treatment with various inotropic agents given alone and simultaneously with acetylcholine. Acetylcholine alone markedly elevated cyclic GMP levels but did not substantially change myocardial contractility. However, the same concentration of acetylcholine significantly attenuated the inotropic effect of isoproterenol and histamine, two drugs that may act by increasing myocardial levels of cyclic AMP. The decrease in the inotropic response to isoproterenol did not appear to be due to a decrease in the generation of cyclic AMP, because cyclic AMP levels were similar in hearts receiving isoproterenol alone and those receiving isoproterenol with acetylcholine. Dibutyryl cyclic GMP also antagonized the inotropic action of isoproterenol. Acetylcholine did not alter the inotropic effects of ouabain, an agent that increases myocardial contractility without changing cyclic AMP levels. These results suggest that cyclic GMP mediates the antiadrenergic effects of acetylcholine by specifically antagonizing the inotropic actions of cyclic AMP.• Histological studies done since the early 1960s have documented the presence of cholinergic innervation in the ventricular myocardium (1, 2). In addition, a number of physiological experiments have demonstrated that stimulation of vagal nerves or administration of cholinergic drugs can depress, although often minimally, the contractile state of the ventricle (3-7). The ventricular depressant effect of the cholinergic system appears to be enhanced in the presence of adrenergic stimulation (8-13). This complex interaction between adrenergic and cholinergic effects on the heart, in which the cholinergic depressant action is magnified during sympathetic stimulation, has been termed accentuated antagonism by Levy (14).Several studies, all done with broken cell preparations or tissue slices, have also shown that cholinergic drugs can attenuate catecholamineinduced increases in cyclic adenosine monophosphate (AMP) levels in cardiac tissues (15,16 attenuation of the amount of cyclic AMP generated has logically been proposed as the mechanism, at the subcellular level, for the antagonism between the adrenergic and the cholinergic systems. With the recent demonstration that the level of cyclic guanosine monophosphate (GMP) in the myocardium is increased after cholinergic stimulation (16,17), it became of interest to investigate whether the interaction of the adrenergic and cholinergic systems at the subcellular level of the heart is occurring between cyclic AMP and cyclic GMP. The series of experiments reported in this paper was performed with the objective of attempting to correlate the contractile state of intact ventricular muscle with induced changes in cyclic nucleotide (cyclic AMP and cycl...

show abstract

“…It is concluded that 5-HT in low concentrations acts as a weak agonist at the cholinoceptive receptors and therefore blocks the action of acetylcholine. Furthermore, nicotine and larger doses of 5-HT have actions on ganglionic structures and liberate acetylcholine, which in turn releases catecholamines.Although acetylcholine is known to have a negative inotropic action on isolated rabbit, atria, Hoffmann, Hoffmann, Middleton & Talesnik (1945) demonstrated that it produces stimulation in the presence of atropine and that this action is due to the release of catecholamines. Trendelenburg (1960) analysed the action of 5-hydroxytryptamine (5-HT) on isolated rabbit atria and postulated that 5-HT produced its effects through an action on neural elements in the atrial tissue.…”

mentioning

confidence: 99%

“…Although acetylcholine is known to have a negative inotropic action on isolated rabbit, atria, Hoffmann, Hoffmann, Middleton & Talesnik (1945) demonstrated that it produces stimulation in the presence of atropine and that this action is due to the release of catecholamines. Trendelenburg (1960) analysed the action of 5-hydroxytryptamine (5-HT) on isolated rabbit atria and postulated that 5-HT produced its effects through an action on neural elements in the atrial tissue.…”

mentioning

confidence: 99%

Interactions between acetylcholine, 5‐hydroxytryptamine, nicotine and morphine on isolated rabbit atria

Chittal

Dadkar

Aitondé

1968

British J Pharmacology

View full text Add to dashboard Cite

1. The effects of 5-hydroxytryptamine (5-HT) and morphine on the responses to acetylcholine and nicotine of isolated rabbit atria were studied. 2. 5-Hydroxytryptamine (10 ug/ml.) and morphine (20 jug/ml.) blocked the negative chronotropic and inotropic actions of acetylcholine.3. Nicotine (20 ,ug/ml.) produced stimulation of the atria, which was blocked by dichlorisoprenaline, morphine, 5-HT, bretylium and hemicholinium. Hemicholinium block was reversed by choline.4. In reserpinized preparations, nicotine produced inhibition of atria and this action was also blocked by atropine, 5-HT and morphine. Inhibition induced by nicotine was potentiated by physostigmine. 5. 5-Hydroxytryptamine (20 ug/ml.) produced stimulation of atria. This was blocked by bretylium and reduced by hemicholinium. Hemicholinium block was reversed by choline. 6. It is concluded that 5-HT in low concentrations acts as a weak agonist at the cholinoceptive receptors and therefore blocks the action of acetylcholine. Furthermore, nicotine and larger doses of 5-HT have actions on ganglionic structures and liberate acetylcholine, which in turn releases catecholamines.Although acetylcholine is known to have a negative inotropic action on isolated rabbit, atria, Hoffmann, Hoffmann, Middleton & Talesnik (1945) demonstrated that it produces stimulation in the presence of atropine and that this action is due to the release of catecholamines. Trendelenburg (1960) analysed the action of 5-hydroxytryptamine (5-HT) on isolated rabbit atria and postulated that 5-HT produced its effects through an action on neural elements in the atrial tissue. Jacob & Poite-Bevierre (1960) have shown that 5-HT has three successive phases of action on the isolated rabbit heart. The negative chronotropic and inotropic actions of 5-HT were shown to be blocked by atropine by these workers. In view of this, a study on the interactions of 5-HT and acetylcholine on isolated rabbit atria was undertaken. We have shown in the present investigation that 5-HT, in concentrations that fail to produce any discernible effects, influences the action of acetylcholine and nicotine on the atria.

show abstract

The Stimulating Effect of Acetylcholine on the Mammalian Heart and the Liberation of an Epinephrine-Like Substance by the Isolated Heart

Cited by 140 publications

References 0 publications

Some Aspects of the Pharmacology of an Homologous Series of Choline Esters of Fatty Acids

Some Aspects of the Pharmacology of an Homologous Series of Choline Esters of Fatty Acids

Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium.

Interactions between acetylcholine, 5‐hydroxytryptamine, nicotine and morphine on isolated rabbit atria

Contact Info

Product

Resources

About