Release of Metaraminol (Aramine) from the Heart by Sympathetic Nerve Stimulation

Crout, J. Richard; Alpers, Hilma S.; Tatum, E. L.; Shore, Parkhurst A.

doi:10.1126/science.145.3634.828

Cited by 85 publications

(29 citation statements)

References 6 publications

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“…Consistent with this are the findings of Crout, Alpers, Tatum & Shore (1964), who have recently reported that sympathetic nerve stimulation can release metaraminol from the hearts of the animals previously treated with metaraminol. Their study and this one provide pharmacological evidence that metaraminol is bound in the nerve endings at sites ordinarily occupied by noradrenaline.…”

Section: Discussionsupporting

confidence: 84%

Restoration of the Response to Tyramine by Metaraminol in Reserpinized Cats

Bhagat

Bovell

Ragland

1966

British Journal of Pharmacology and Chemotherapy

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It is well known that depletion of the noradrenaline stores by treatment of animals with reserpine reduces or abolishes the response to tyramine. However, the response to tyramine may be restored by infusion of noradrenaline. This restoration is believed to be due to a partial refilling of the previously depleted stores with exogenous noradrenaline and a subsequent release by tyramine.It has been shown that a-methylmetatyrosine is decarboxylated to form a-methylmetatyramine (Udenfriend & Zaltzman-Nirenberg, 1962). The metabolism proceeds further to form the active product metaraminol. This amine may enter the noradrenaline storage site and take over the function of neurochemical transmitter .The present study was undertaken to determine whether or not metaraminol can restore the response to tyramine in reserpinized cats. METHODSCats of either sex and of 2.0 to 3.5 kg body weight were used. After induction of anaesthesia with ether spinal preparations were made according to the method of Burn (1952). The movement of the nictitating membrane was recorded with an isotonic myograph; the weight on the nictitating membrane was 5 g. The blood pressure was recorded from a femoral artery with a pressure transducer (Linear-Core model P-1000).Cats were administered 1.25 mg/kg of reserpine (Serpasil, Ciba) 24 hr before the experiments. Disulfiram (200 mg/kg) was administered intraperitoneally as a suspension 1 hr before the injection of a-methylmetatyramine or metaraminol.The following substances were used: a-methylmetatyrosine, DL-a-methylmetatyramine, a-methylnoradrenaline hydrochloride, metaraminol bitartrate and tyramine hydrochloride. The details of dosage and routes of administration are given in Results. RESULTSRestoration of the response to tyramine by a-methylnoradrenaline or metaraminol. Infusions of either 1 mg of a-methylnoradrenaline or 0.5 mg of metaraminol during a 30-min period restored the action of tyramine on the blood pressure and on the nictitating membrane in the reserpinized cat ( Figs. 1 and 2).

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Section: Discussionsupporting

confidence: 84%

Restoration of the Response to Tyramine by Metaraminol in Reserpinized Cats

Bhagat

Bovell

Ragland

1966

British Journal of Pharmacology and Chemotherapy

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“…In the present investigation, an attempt was X Present Address: Medical Research Department, Hoffman-LaRoche & Co., Basel, Switzerland. made to characterize further these organ differences by comparing the release from brain and heart slices of metaraminol, a noradrenaline congener which acts as a non-metabolizable false transmitter at adrenergic nerve endings (Shore, Busfield & Alpers, 1964;Crout, Alpers, Tatum & Shore, 1964 30-60 mg) was used; with heart studies, a ventricle slice (0.3 mm, 60-80 mg) was used. Tissue slices were placed in 20 ml beakers containing 3 ml Krebs-Ringer bicarbonate buffer (pH 7.4) and bubbled with 95% 02 and 5% CO2 (Dengler, Michaelson, Spiegel & Titus, 1962 (Baldessarini & Kopin, 1967).…”

Section: Introductionmentioning

confidence: 99%

Differences in Amine Storage in Rat Heart and Brain

Enna

Shore

1974

British J Pharmacology

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1 The characteristics of storage of amphetamine-releasable amine in rat heart and brain were studied in vitro with labelled and unlabelled metaraminol 5 The (+)-isomer of amphetamine released three to four times more [3 HI -MA from brain slices than did the (-)-isomer, while the isomers were equipotent with regard to [3 HI-MA release from heart slices. 6 Amphetamine-induced [3 HI -MA release from heart slices was unaffected by the presence of ca-methyl-p-tyrosine, while release from brain slices was inhibited. 7 On the basis of the foregoing results it appears that amine storage differs in brain and heart, with brain exhibiting more than one functional amine pool.

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“…The metabolic fate of a-methyldopa and a-methyl-m-tyrosine being similar, the corresponding false neurotransmitters would be a-methylnoradrenaline (Muscholl & Maitre, 1963;Day & Rand, 1964) and metaraminol (Weissbach, 0. D. Gulati, H. M. Parikh, S. Y. Ringe and M. L. Sherlekar Lovenberg & Udenfriend, 1960;Lovenberg, Weissbach & Udenfriend, 1962;Crout & Shore, 1964) respectively. It has been demonstrated by Bejrablaya, Burn & Walker (1958), Burn & Rand (1958, 1960 and by numerous other investigators that dopa, dopamine and noradrenaline are able to restore the sympathomimetic action of tyramine in reserpine pretreated animals.…”

Section: Introductionmentioning

confidence: 99%

An investigation of α‐methyl amino‐acids and their derivatives on isolated tissue preparations

Gulati

Parikh

Ringe

et al. 1970

British J Pharmacology

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Summary1. The ability of a-methyl amino-acids and their corresponding amines to restore the sympathomimetic actions of tyramine, and the uptake of the aminoacids and the amines, were studied in isolated tissue preparations obtained from reserpine pretreated animals. 2. Tyramine relaxed isolated rat ileum preparations from non-reserpinized rats but not from reserpine treated animals. a-Methyldopa, a-methylnoradrenaline and lower concentrations of metaraminol restored the responses of reserpinized preparations. a-Methyldopamine, a-methyl-m-tyrosine, a-methylp-tyrosine and higher concentrations of metaraminol did not do so. The restoring effect of a-methyldopa was blocked by disulphiram. a-Methyl-ptyrosine or a-methyl-m-tyrosine blocked the restoring action of a-methyldopa but not of a-methylnoradrenaline. Cocaine blocked the restoration of responses to tyramine by a-methylnoradrenaline but not by a-methyldopa. a-Methyldopa and a-methylnoradrenaline failed to restore responses to tyramine in the presence of sodium-free Tyrode solution. 3. Tyramine increased the perfusion pressure in isolated rabbit ear preparations obtained from non-reserpinized animals but was very much less active in preparations obtained from reserpine treated animals. a-Methyldopa, a-methylm-tyrosine, a-methylnoradrenaline, a-methyl-p-tyrosine and metaraminol restored the effects of tyramine. a-Methyldopamine did not do so. The restoring effect of a-methyldopa and a-methyl-m-tyrosine was blocked by disulfiram. a-Methyl-p-tyrosine blocked the restoring effect of a-methyl-mtyrosine. 4. Tyramine produced positive inotropic effects in isolated rabbit heart preparations. This was either reduced or absent in preparations obtained from reserpine pretreated animals. a-Methyldopa, a-methylnoradrenaline, a-methylm-tyrosine and metaraminol restored the responses to tyramine. a-Methyldopam.ne and a-methyl-p-tyrosine did not do so.

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Release of Metaraminol (Aramine) from the Heart by Sympathetic Nerve Stimulation

Cited by 85 publications

References 6 publications

Restoration of the Response to Tyramine by Metaraminol in Reserpinized Cats

Restoration of the Response to Tyramine by Metaraminol in Reserpinized Cats

Differences in Amine Storage in Rat Heart and Brain

An investigation of α‐methyl amino‐acids and their derivatives on isolated tissue preparations

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