The Mode of Action of Reserpine on the Transmembrane Potential of Rabbit’s Atrium in Vitro

Toda, Noboru

doi:10.1254/jjp.12.93

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…However, the dose of reserpine should deplete not only atrial noradrrenaline but also atrial 5-HT, if 5-HT is contained. Though the administration of reserpine to rabbit markedly depleted atrial amines, the response of the atrium to adrenaline or noradrenaline was never depressed by the reserpinization (21). But the positive inotropic and chronotropic re sponses to 5-HT in the present experiments were markedly, depressed by the reserpini zation, similarly shown by the experiments of Cronheim et al (22) that the infusion of 5-HT induced a profound fall of blood pressure in dogs treated with reserpine.…”

Section: Discussionsupporting

confidence: 77%

Effects of 5-Hydroxytryptamine on the Isolated Atrium of Rabbit

Toda

1963

Japanese Journal of Pharmacology

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There have been numerous observations to suggest that in mammals 5-hydroxy tryptamine acts as a humoral agents (1, 2). Though 5-HT is very widespread in the body, there has been no literature to show the amount of 5-HT in the heart of the mammals. But in the cyclostome heart it has been shown that the amount of 5-HT is (6). The latter authors confirmed that 5-HT, in concentration of 10-6, had a powerful stimulant action on the isolated auricle.Stimulation was, however, preceded by a slight and transient inhibition and followed by a marked depression. Atropine could abolish the initial inhibiting effect, but not subsequent one. Studies on the isolated papillary muscle of rabbit (7) suggested that 5-HT did not increase the strength of contraction.The results obtained from the isolated auricle of rabbit suggest that 5-HT may exert triphasic or polyphasic action.The effects of 5-HT on the transmission of nerve impulses in the autonomic nervous system has been explored by several investigators. Reversible blockade of the ganglionic transmission by relatively large dose of 5-HT was demonstrated by Marrazzi et al. (8) and Douglas et al. (9). However, the intra-arterial injection of small dose of 5-HT potentiated the response of postsynaptic fibers and of the end organ to electrical stimula tion of the cervical sympathetic nerve (10) and increased the spontaneous activity of the postganglionic structures (11). The similar potentiating effect of 5-HT on the transmission of the isolated stellate ganglion of rat was demonstrated by Hertzler (12).It was, therefore, of interest to see whether 5-HT affected the transmembrane potential of the atrium or not. If it affects, it will be of value to see the mode of action of 5-HT on the transmembrane potential. METHODSSeventy albino rabbits of either sex, weighing 1.5 to 2.5 kg, were killed by bleeding through cutting the both common carotid arteries.Immediately thereafter, the thorax was para-sternally opened. The whole heart was extirpated and immersed in warmed

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Section: Discussionsupporting

confidence: 77%

Effects of 5-Hydroxytryptamine on the Isolated Atrium of Rabbit

Toda

1963

Japanese Journal of Pharmacology

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“…Toda (9) of this laboratory observed that the application of monoamine oxidase inhibitors to the isolated rabbit atrium did not reverse, but delayed onset of the effect of reserpine on the atrial transmembrane potential.…”

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confidence: 98%

The Effects of Reserpine on the Spontaneous Contraction of the Isolated Atrium of Rabbit Treated With Monoamine Oxidase Inhibitors

Tachi

Nakatani

Fujiwara

1963

Japanese Journal of Pharmacology

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The depressant effect of reserpine on the spontaneous contraction and transmem brane potentials of the isolated atrial preparation of rabbit has been described in detail in the previous reports (1-4). A rise instead of fall in the blood pressure due to reserpine, the reserpine reversal, was demonstrated in the dog and cat pretreated with monoamine oxidase inhibitors (5, 6). Shore and Brodie (7) found that administration of reserpine to rabbits pretreated with iproniazid resulted in the sympathetic excite ment. However, Eltherington and Horita (6) observed no sign of the reserpine reversal after amphetamine in mice. Shimamoto and Torii (8) observed that pretreatment of rabbits with iproniazid reversed the response of the blood pressure and the behavior to the intravenous injection of reserpine.Toda (9) of this laboratory observed that the application of monoamine oxidase inhibitors to the isolated rabbit atrium did not reverse, but delayed onset of the effect of reserpine on the atrial transmembrane potential.Recently, Goldberg and Shideman (10) have shown that the intraperitoneal injection of a monoamine oxidase inhibitor, SKF-385, depletes the myocardial noradrenaline in cats, and conversely, accumulates it in rats. Matsuo (11) . of this laboratory has shown that the application of SKF-385 to the isolated atrium of rabbit does not produce sig nificant changes in the noradrenaline content of the atria. Pepeu et al. (12) demonstrated that the pretreatment of the guinea-pig atrium with iproniazid prevented the spon taneous depletion of noradrenaline from this tissue, but that with PIH did not so.To elucidate the mechanism of the reserpine reversal on the spontaneous contraction of the isolated atrial preparation of rabbits, the effects of the monoamine oxidase inhibitors on the depressant action of reserpine were studied. METHODSAlbino rabbits, 2.0 to 2.5 kg of body weight, were used. Animals were killed by cutting both common carotid arteries. Immediately thereafter the heart was extirpated, and the atrium was separated from the ventricle.The atrial preparation was

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“…Shideman et al (1) and Horita et al (3) have concluded that the sympathomimetic effects of SKF-385 as well as phenyl-isopropyl hydrazine (Catron) derived from the release of endogenous noradrenaline rather than from the inhibitory effect of the drugs on the monoamine oxidase. The adrenaline-like stimulating effects of SKF-385 on the isolated auricular preparation of rabbit (Toda, unpublished) and on the transmembrane potentials of the isolated atrium of rabbit (4) have been confirmed in this laboratory. Toda and Tachi also showed that the administration of SKF-385 retarded the manifestation of the depressive effects of re3erpine on the rhythmical con traction and the action potential of the isolated atrium.…”

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confidence: 62%