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Uptake, metabolism and release of [ 3 H]‐adrenaline by human platelets
Author(s) -
BORN G. V. R.,
SMITH J. B.
Publication year - 1970
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1970.tb09903.x
Subject(s) - metabolite , chemistry , metabolism , phentolamine , reserpine , platelet , endocrinology , monoamine oxidase , medicine , biochemistry , enzyme , biology , receptor
Summary1 Measurements were made of the uptake, metabolism and release of [ 3 H]‐adrenaline by human platelets in citrated plasma or in an artificial medium. 2 Radioactive adrenaline was not taken up at 0–2° C. At 37° C there was a slow uptake which continued for at least 5 hours. 3 About half of the radioactivity in the platelets was intact adrenaline. The other half was an acidic metabolite from which adrenaline was released by acid hydrolysis. 4 The immediate uptake of adrenaline was proportional to its concentration in the plasma up to at least 1 × 10 −5 m . Uptake measured after 1 h also increased linearly with concentration up to about 1 × 10 −4 m but less with higher concentrations. The highest concentration ratio was about 12. 5 The concentration of metabolite in the platelets increased with the concentration of added adrenaline only up to about 2 × 10 −4 m . 6 The immediate uptake of adrenaline was partially inhibited by phentolamine and dihydroergotamine. Measurement of uptake both immediately and after 1 h showed that the inhibition produced was not increased beyond about 50% by these drugs or by (±)‐propranolol, chlorpromazine or amitriptyline up to 1 × 10 −4 m . 7 Formation of the metabolite was inhibited by pyrogallol, 8‐hydroxyquinoline, or tropolone. This inhibition was associated with a corresponding increase in the adrenaline accumulated intact. Formation of the metabolite was not inhibited by monoamine oxidase inhibitors. 8 Reserpine caused a small decrease in the uptake of adrenaline radioactivity in 1 h and a great increase in the proportion recovered as metabolite. 9 Thrombin caused the release from platelets of intact adrenaline but not of the metabolite. 10 Platelets of albino patients with spontaneous haemorrhages accumulated adrenaline radioactivity at the normal rate but this radioactivity was wholly accounted for by metabolite and not released by thrombin. 11 After taking up adrenaline, platelets resuspended in artificial medium at 37° C slowly released both adrenaline and its metabolite. At the same time, the intracellular adrenaline was slowly metabolized. 12 The results suggest that human platelets take up adrenaline by two processes, one of which is inhibited by both α‐ and β‐adrenoceptor blocking agents as well as by phenothiazines; and that in the platelets adrenaline is partly stored in organelles from which, like 5‐hydroxytryptamine, it can be specifically released.