Subcellular Distribution of [14C]5-Hydroxytryptamine in the Blood Platelets of Rabbits: Effects of Imipramine and Haloperidol

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Abstract
Long-term (10 days) administration of imipramine [20 mg/(kg .times. d [density])] to rabbits significantly increases the Km value (4.0 .mu.M0 of 5-hydroxytryptamine uptake in their platelets compared to those of saline- (0.7 .mu.M) or haloperidol- (0.4 .mu.M) treated rabbits. Administration of haloperidol inhibits the 5-hydroxytryptamine uptake non-competitively, and in vitro it had an ID50 [median inhibitory dose] value of 22 .mu.M. I.v. injections of [14C]5-hydroxytryptamine were given to the animals 1 h before blood collection. After isolation of platelets, their sonicates were subjected to 30-60% continuous sucrose gradient centrifugation. The subcellular distribution of [14C]5-hydroxytryptamine indicates that imipramine treatment, in contrast to the control and haloperidol treatment, led to a shift in the exogenous 5-hydroxytryptamine peak from within the granular zone (d 1.18) to the extragranular cytoplasm (d 1.15). Compared to control values, the imipramine treatment caused 63% inhibition in the platelet Na+-K+-ATPase [EC 3.6.1.3] activity. Haloperidol and imipramine have been used to block dopaminergic receptors.