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In Vitro Uptake of Benzodiazepines by Rat Pineal Gland
Author(s) -
Lowenstein Pedro R.,
Solveyra César González,
Cardinali Daniel P.
Publication year - 1984
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1984.tb00212.x
Subject(s) - pineal gland , in vitro , melatonin , pharmacology , biology , medicine , endocrinology , biochemistry
As a part of a study aiming to characterize the physiological and pharmacological significance of the high affinity pineal benzodiazepine (BZP) binding sites reported previously, we examined the uptake of the BZP derivative 3 H‐flunitrazepam (FNZP) by rat pineal glands in vitro. At 37 °C, 3 H‐radioactivity was taken up by tissue up to a pineal/medium concentration of about 12, while at 0 °C the uptake amounted to only one‐third that at 37 °C. Reciprocal of uptake analyzed by Lineweaver‐Burk plots indicated apparent K m 's of 1.74 and 1.45 μM, and V max 's of 1.32 and 1.04 pmol per min per mg tissue, for control and superior cervical ganglionectomized rats, respectively, suggesting that the neural compartment does not participate significantly in 3 H‐FNZP uptake. Cerebral cortex explants of similar size and weight as the pineal ones took up 3 H‐FNZP to a maximum tissue/ medium concentration of about 2. Neither pineal nor cerebral cortex 3 H‐radioactivity uptake exhibited significant changes as a function of time of day. A number of agents, including several BZP analogues, cocaine, desipramine, melatonin, fluoxetine, nomifensine, and dipiridamol, as well as changes in the ionic environment or metabolic inhibitors, did not affect 3 H‐FNZP uptake significantly. Other tissues, such as liver, muscle, kidney, adrenal gland, or anterior pituitary, took up 3 H‐radioactivity to tissue concentrations slightly lower than those of the cerebral cortex, suggesting that drug liposolubility accounted only to a limited extent for the high in vitro uptake detected in incubated pineals.