Dopamine (3-hydroxytyramine) replacement and metabolism in sympathetic nerve and adrenal medullary depletions after prolonged thermal injury.
After severe thermal injury, the adrenal medulla and the sympathetic nerves can be partially or totally depleted of their adrenaline (epinephrine) and noradrenaline (norepinephrine). The purpose of this paper is to elucidate the rate at which dopamine-2-(14)C, a precursor of noradrenaline, is synthesized into noradrenaline and noradrenaline metabolic products, thereby giving some indication as to dopamine's utilization, turnover, and possible use in treating such noradrenaline-adrenaline depletions. Three burned subjects, 3 wk postburn, were infused with 104.6 muc (872 mug) of dopamine-2-(14)C for 4 hr. Urine was collected at various hourly intervals for the 1st day, and thereafter for 4 days, assayed, and compared with the metabolism of dopamine in normal subjects. Methods for separating, identifying, and counting radioactivity of the various metabolic products of dopamine are described. Normally 87.6 +/-3.1% of the total radioactivity is recovered within 24 hr after an infusion of dopamine-2-(14)C, but in the three severely burned patients, this value was increased to 93.1, 97.3, and 97.5% in 24 hr. There was a marked decrease in the percentage of radioactivity recovered as noradrenaline in all collection periods, and in contrast to normal subjects, no radioactive noradrenaline was recovered after 24 hr. Concomitantly, there was an increase in radioactivity recovered as metabolic products of noradrenaline, reflecting a compensatory shift toward noradrenaline synthesis and utilization at the expense of the dopamine metabolic products. The results indicate that in the burned patients the infused dopamine-2-(14)C was rapidly synthesized into noradrenaline and then rapidly released and metabolized. From these results it seems evident that dopamine would be a useful adjunct in the treatment of sympathico-adrenal medullary depletion in burns.
D000313:Adrenal Medulla / Q000378:metabolism*; D000308:Adrenocortical Hyperfunction / Q000188:drug therapy; D002056:Burns / Q000188:drug therapy / Q000378:metabolism*; D002247:Carbon Isotopes; D004298:Dopamine / Q000378:metabolism* / Q000627:therapeutic use; D004837:Epinephrine / Q000096:biosynthesis; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis; D013153:Splanchnic Nerves / Q000378:metabolism*
D002247:Carbon Isotopes; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine
Acta Physiol Scand. 1963 May;58:77-89
13971782
J Clin Endocrinol Metab. 1954 Jun;14(6):608-21
13163142
J Clin Invest. 1960 Dec;39:1927-32
13706989
Circulation. 1968 Sep;38(3):592-603
5673610
Health Phys. 1968 Mar;14(3):199-203
5637393
Ann Surg. 1965 Nov;162(5):893-900
17859795
Ann Surg. 1957 Apr;145(4):479-87
13412024
J Clin Invest. 1962 Feb;41:197-202
13900260
Biochem Pharmacol. 1968 Jun;17(6):905-14
5661353