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Displacement of norepinephrine from the rat heart by14C-metaraminol

Biochemical Pharmacology
Publication Date
DOI: 10.1016/0006-2952(67)90009-3


Abstract Rats were injected with submaximal quantities (0.24 mg/kg) of 14C-metaraminol, i.e. enough to lower the concentration of norepinephrine in the heart by about 60 per cent, measured 18 hr after drug administration. In the ventricles at 18,42 and 66 hr after metaraminol injection and in the atria at the two latter times, radioactivity was present in amounts sufficient to account exactly for the norepinephrine missing, on a mole-for-mole displacement basis. Atrial radioactivity 18 hr after metaraminol administration was insufficient to account for the whole of the missing catecholamine. Possibly at 18 hr a steady state had not been reached in the atria, an interpretation which is strengthened by the fact that other catecholamines (epinephrine and dopamine) were present only in trace amounts. Chemically determined metaraminol was consistently less than indicated by radiocounting. Even though no evidence was gained for the presence of 14C-α-methylnorepinephrine in the tissue, it is possible that metabolites of metaraminol account for part of the norepinephrine displacement observed. The administration of larger amounts of 14C-metaraminol (3 mg/kg) resulted in catecholamine depletion greater than that accounted for by radio-activity in the tissue, and this was particularly striking in the atria. Thus, the relationship between tissue radio-activity and norepinephrine concentration depends upon several factors, and only under certain conditions, as described above, is a one-for-one displacement of the catecholamine clearly demonstrated.

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