Accumulation of dopamine by blood platelets from normal subjects and parkinsonian patients under treatment with l‐DOPA

Abstract

Summary ,1. Human blood platelets have been shown to take up dopamine by an energydependent, saturable process that is inhibited by 5-hydroxytryptamine (5-HT), desipramine and other drugs. 2. Platelets from parkinsonian subjects receiving oral L-DOPA also took up dopamine.3. When the responses of normal and parkinsonian platelets were compared, the parkinsonian cells showed the following differences: increased affinity for the dopamine transport process; decreased equilibrium concentrations of dopamine after incubation for 90 min, and greater efflux of dopamine from loaded platelets during a 10 min incubation. 4. There were no differences in the uptake of 5-HT by parkinsonian platelets, but endogenous 5-HT was significantly reduced; ATP was normal. 5. In two out of three samples of platelets from parkinsonian subjects, traces of a dopamine-like substance were detected, but this finding requires confirmation. 6. If the platelet is a valid model for dopaminergic brain neurones, then the results described would suggest that dopamine uptake and storage may be abnormal in brain neurones in Parkinson's disease.

Content and Subcellular Localization of Catecholamines and 5‐hydroxytryptamine in Human and Animal Blood Platelets: Monoamine Distribution Between Platelets and Plasma

“…For instance, it was found that labelled CA injected into rabbits, were highly concentrated in a platelet fraction rich in 5-HT organelles (Da Prada & Pletscher, 1969b). In addition it has been shown that isolated platelets take up CA in vitro (Born et al, 1958;Weissbach et al, 1958;Weil-Malherbe & Bone, 1958;Born & Smith, 1970;Boullin & O'Brien, 1970) and that 5-HT organelles isolated from rabbit platelets are also able to concentrate labeled CA in vitro (Da Prada & Pletscher, 1969a). Born & Smith (1970) have demonstrated that reserpine, which reduces 5-HT uptake by acting at the level of the 5-HT granular membrane (Pletscher, Burkard & Tranzer, 1967;Da Prada & Pletscher, 1969b), also impairs Ad uptake in intact platelets.…”

“…Indirect experimental evidence indicates that 5-HT organelles might also be the storage sites for platelet CA (Born, Hornykiewicz & Stafford, 1958;Weissbach, Bogdanski & Udenfriend, 1958;Weil-Malherbe & Bone, 1958;Hughes & Brodie, 1959;Born & Smith, 1970;Boullin & O'Brien, 1970). However, the very low amounts of CA present in the platelets and the consequent methodological difficulties of their measurement account for the lack of data regarding content and localization of platelet adrenaline (Ad), noradrenaline (NA) and dopamine.…”

Uptake of dopamine by platelets in vivo

“…This phenomenon seems to occur in vivo in man, since we found a dopamine-like substance in the platelets of the patients with Parkinson's disease who received oral L-dopa (Boullin & O'Brien, 1970). We have now explored in vivo uptake of dopamine further by infusing 14C-dopam.ine into cats.…”

“…Electron microscopy of the 20,000 g pellet used for preparation of the sucrose density gradient showed a population of subcellular particles including endoplastic reticulum, a-granules, dense-cored storage organelles, and some mitochondria. Maynert & Isaac (1968) (Boullin & O'Brien, 1970).…”

“…Other experimental details are given in the earlier paper (Boullin & O'Brien, 1970). Dopamine was separated from metabolites by the method of Robinson, Lovenberg, Keiser & Sjoerdsma (1968).…”