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. 1969 May;36(1):153–160. doi: 10.1111/j.1476-5381.1969.tb08312.x

Regulation of metaraminol efflux from rat heart and salivary gland

E Costa, N H Neff, S H Ngai
PMCID: PMC1703577  PMID: 5768085

Abstract

1. The turnover rate of noradrenaline (NA) in heart and submaxillary salivary gland was studied in rats exposed to 4° C or maintained at room temperature (22° C). Cold exposure increased the turnover of the NA store in heart but not in salivary gland.

2. In another series of experiments the decline of metaraminol (M) from heart and submaxillary salivary gland was studied in rats exposed to 4° C or maintained at room temperature. Cold exposure accelerated the efflux of M from heart, but not from salivary gland. It is concluded that the accelerated decline of M from heart is the consequence of selective activation of the sympathetic nerves that innervate the heart.

3. The turnover of NA was studied in rat heart after the administration of M (100 μg/kg intravenously) or its precursor α-methyl-meta-tyrosine (200 mg/kg intraperitoneally). Turnover remained essentially normal after these drugs.

4. The administration of desipramine (DMI, 20 mg/kg intraperitoneally) 1 hr after M (100 μg/kg intravenously) induced a rapid sustained efflux of M from heart and salivary gland. The results of this study suggest that the slow decline of M from heart is the result of the great affinity of the amine retrieval mechanism in sympathetic nerve endings for M. DMI inhibits the retrieval mechanism, thus accelerating the efflux of M.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Almgren O., Waldeck B. On the disposition of [3H]metaraminol in the rat salivary gland. J Pharm Pharmacol. 1967 Nov;19(11):705–708. doi: 10.1111/j.2042-7158.1967.tb08020.x. [DOI] [PubMed] [Google Scholar]
  2. BROWN G. L., GILLESPIE J. S. The output of sympathetic transmitter from the spleen of the cat. J Physiol. 1957 Aug 29;138(1):81–102. doi: 10.1113/jphysiol.1957.sp005839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brodie B. B., Costa E., Dlabac A., Neff N. H., Smookler H. H. Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines. J Pharmacol Exp Ther. 1966 Dec;154(3):493–498. [PubMed] [Google Scholar]
  4. CARLSSON A., LINDQVIST M. In-vivo decarboxylation of alpha-methyl DOPA and alpha-methyl metatyrosine. Acta Physiol Scand. 1962 Jan;54:87–94. doi: 10.1111/j.1748-1716.1962.tb02331.x. [DOI] [PubMed] [Google Scholar]
  5. COSTA E., GESSA G. L., HIRSCH C., KUNTZMAN R., BRODIE B. B. On current status of serotonin as a brain neurohormone and in action of reserpinelike drugs. Ann N Y Acad Sci. 1962 Jan 13;96:118–133. doi: 10.1111/j.1749-6632.1962.tb50107.x. [DOI] [PubMed] [Google Scholar]
  6. Carlsson A., Fuxe K., Hamberger B., Lindqvist M. Biochemical and histochemical studies on the effects of imipramine-like drugs and (+)-amphetamine on central and peripheral catecholamine neurons. Acta Physiol Scand. 1966 Jul-Aug;67(3):481–497. doi: 10.1111/j.1748-1716.1966.tb03334.x. [DOI] [PubMed] [Google Scholar]
  7. Carlsson A., Waldeck B. Rapid release of 3H-metaraminol induced by combined treatment with protriptyline and reserpine. J Pharm Pharmacol. 1965 May;17(5):327–328. doi: 10.1111/j.2042-7158.1965.tb07678.x. [DOI] [PubMed] [Google Scholar]
  8. Costa E., Boullin D. J., Hammer W., Vogel W., Brodie B. B. Interactions of drugs with adrenergic neurons. Pharmacol Rev. 1966 Mar;18(1):577–597. [PubMed] [Google Scholar]
  9. DENGLER H. J., SPIEGEL H. E., TITUS E. O. Effects of drugs on uptake of isotopic norepinephrine by cat tissues. Nature. 1961 Aug 19;191:816–817. doi: 10.1038/191816a0. [DOI] [PubMed] [Google Scholar]
  10. GESSA G. L., COSTA E., KUNTZMAN R., BRODIE B. B. On the mechanism of norepinephrine release by alpha-methyl-metaty-rosine. Life Sci. 1962 Aug;1:353–360. doi: 10.1016/0024-3205(62)90059-0. [DOI] [PubMed] [Google Scholar]
  11. Gordon R., Spector S., Sjoerdsma A., Udenfriend S. Increased synthesis of norepinephrine and epinephrine in the intact rat during exercise and exposure to cold. J Pharmacol Exp Ther. 1966 Sep;153(3):440–447. [PubMed] [Google Scholar]
  12. Johnson G. E., Mickle D. The influence of cold exposure on the in vivo release of metaraminol. Br J Pharmacol Chemother. 1966 Nov;28(2):246–254. doi: 10.1111/j.1476-5381.1966.tb01891.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnson G. E., Pugsley T. A. The formation and release of metaraminol during exposure to warm or cold environments. Br J Pharmacol. 1968 Oct;34(2):267–276. doi: 10.1111/j.1476-5381.1968.tb07050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maître L., Staehelin M. On the norepinephrine replacement by alpha-methyl-norepinephrine in the rat heart after treatment with alpha-methyl-DOPA. Experientia. 1967 Oct 15;23(10):810–811. doi: 10.1007/BF02146855. [DOI] [PubMed] [Google Scholar]
  15. Neff N. H., Costa E. The influence of monoamine oxidase inhibition on catecholamine synthesis. Life Sci. 1966 May;5(10):951–959. doi: 10.1016/0024-3205(66)90204-9. [DOI] [PubMed] [Google Scholar]
  16. Oliverio A., Stjärne L. Acceleration of noradrenaline turnover in the mouse heart by cold exposure. Life Sci. 1965 Dec;4(23):2339–2343. doi: 10.1016/0024-3205(65)90258-4. [DOI] [PubMed] [Google Scholar]
  17. SHORE P. A., ALPERS H. S. FLUOROMETRIC ESTIMATION OF METARAMINOL AND RELATED COMPOUNDS. Life Sci. 1964 Jun;3:551–554. doi: 10.1016/0024-3205(64)90165-1. [DOI] [PubMed] [Google Scholar]
  18. SHORE P. A., BUSFIELD D., ALPERS H. S. BINDING AND RELEASE OF METARAMINOL: MECHANISM OF NOREPINEPHRINE DEPLETION BY ALPHA-METHYL-M-TYROSINE AND RELATED AGENTS. J Pharmacol Exp Ther. 1964 Nov;146:194–199. [PubMed] [Google Scholar]
  19. Shore P. A. The mechanism of norepinephrine depletion by reserpine, metaraminol and related agents. The role of monoamine oxidase. Pharmacol Rev. 1966 Mar;18(1):561–568. [PubMed] [Google Scholar]
  20. Spector S., Gordon R., Sjoerdsma A., Udenfriend S. End-product inhibition of tyrosine hydroxylase as a possible mechanism for regulation of norepinephrine synthesis. Mol Pharmacol. 1967 Nov;3(6):549–555. [PubMed] [Google Scholar]
  21. TRENDELENBURG U., MUSKUS A., FLEMING W. W., de la GOMEZ ALONSO SIERRA B. Effect of cocaine, denervation and decentralization on the response of the nictitating membrane to various sympathomimetic amines. J Pharmacol Exp Ther. 1962 Nov;138:181–193. [PubMed] [Google Scholar]
  22. Weiner N., Selvaratnam I. The effect of tyramine on the synthesis of norepinephrine. J Pharmacol Exp Ther. 1968 May;161(1):21–33. [PubMed] [Google Scholar]

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