TY - JOUR T1 - SUBCELLULAR DISTRIBUTION OF RESERPINE IN BLOOD PLATELETS: EVIDENCE FOR MULTIPLE POOLS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 164 LP - 171 VL - 191 IS - 1 AU - S. J. Enna AU - M. Da Prada AU - A. Pletscher Y1 - 1974/10/01 UR - http://jpet.aspetjournals.org/content/191/1/164.abstract N2 - After i.v. administration, 3H-reserpine accumulated in blood platelets showed an initial rapid decrease between ½ and 6 hours. Thereafter, the 3H-reserpine content remained virtually constant through day 5 followed by another marked diminution which was accompanied by a gradual recovery of the 5-hydroxytryptamine (5-HT). The 5-HT organelles isolated from the platelets showed a similar time course of the 3H-reserpine disappearance except that no initial rapid decrease occurred. Pretreatment with unlabeled reserpine interfered with the accumulation of 2H-reserpine in whole platelets and 5-HT organelles, whereas administration of the unlabeled after the labeled drug did not diminsh the level of radioactivity. Imipramine, given shortly before 3H-reserpine, inhibited the accumulation of the labeled drug in the whole platelets during the first ½ hour, but not at later times. The content of 3H-reserpine in the 5-HT organelles was not changed by imipramine. Subcellular distribution experiments indicated a localization of the 3H-reserpine in the membranes of the 5-HT storage granules as well as in other subcellular organelles. Furthermore, platelet survival as measured by 51Cr was identical to that determined by in vitro or in vivo labeling of the platelets with 3H-reserpine. It is concluded that some reserpine initially accumulates reversibly outside the 5-HT granules, but that the bulk of the drug is permanently and irreversibly bound to 5-HT granules as well as to other sites in platelets and probably megakaryocytes. Owing to the permanence of this binding, reserpine might be useful as a tool for measuring platelet survival and for investigations on production of platelets from megakaryocytes. © 1974 by The Williams & Wilkins Company ER -