In Vitro Uptake of Benzodiazepines by Rat Pineal Gland

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 3H‐flunitrazepam (FNZP) by rat pineal glands in vitro. At 37 °C, 3H‐radioact...

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Autores principales: Lowenstein, P.R., Solveyra, C.G., Cardinali, D.P.
Formato: JOUR
Materias:
benzodiazepine uptake
diurnal rhythms
pineal gland
superior cervical ganglionectomy
benzodiazepine
benzodiazepine receptor
radioisotope
animal cell
central nervous system
circadian rhythm
drug accumulation
drug receptor binding
endocrine system
flunitrazepam h 3
nonhuman
pharmacokinetics
pineal body
rat
Animal
Biological Transport
Cerebral Cortex
Female
Flunitrazepam
Kinetics
Organ Specificity
Pineal Gland
Rats
Rats, Inbred Strains
Receptors, GABA-A
Support, Non-U.S. Gov't
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_07423098_v1_n3_p207_Lowenstein
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id todo:paper_07423098_v1_n3_p207_Lowenstein
record_format dspace
spelling todo:paper_07423098_v1_n3_p207_Lowenstein2023-10-03T15:38:22Z In Vitro Uptake of Benzodiazepines by Rat Pineal Gland Lowenstein, P.R. Solveyra, C.G. Cardinali, D.P. benzodiazepine uptake diurnal rhythms pineal gland superior cervical ganglionectomy benzodiazepine benzodiazepine receptor radioisotope animal cell central nervous system circadian rhythm drug accumulation drug receptor binding endocrine system flunitrazepam h 3 nonhuman pharmacokinetics pineal body rat superior cervical ganglionectomy Animal Biological Transport Cerebral Cortex Female Flunitrazepam Kinetics Organ Specificity Pineal Gland Rats Rats, Inbred Strains Receptors, GABA-A Support, Non-U.S. Gov't 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 3H‐flunitrazepam (FNZP) by rat pineal glands in vitro. At 37 °C, 3H‐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 Km's of 1.74 and 1.45 μM, and Vmax'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 3H‐FNZP uptake. Cerebral cortex explants of similar size and weight as the pineal ones took up 3H‐FNZP to a maximum tissue/ medium concentration of about 2. Neither pineal nor cerebral cortex 3H‐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 3H‐FNZP uptake significantly. Other tissues, such as liver, muscle, kidney, adrenal gland, or anterior pituitary, took up 3H‐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. Copyright © 1984, Wiley Blackwell. All rights reserved JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_07423098_v1_n3_p207_Lowenstein
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic benzodiazepine uptake
diurnal rhythms
pineal gland
superior cervical ganglionectomy
benzodiazepine
benzodiazepine receptor
radioisotope
animal cell
central nervous system
circadian rhythm
drug accumulation
drug receptor binding
endocrine system
flunitrazepam h 3
nonhuman
pharmacokinetics
pineal body
rat
superior cervical ganglionectomy
Animal
Biological Transport
Cerebral Cortex
Female
Flunitrazepam
Kinetics
Organ Specificity
Pineal Gland
Rats
Rats, Inbred Strains
Receptors, GABA-A
Support, Non-U.S. Gov't
spellingShingle benzodiazepine uptake
diurnal rhythms
pineal gland
superior cervical ganglionectomy
benzodiazepine
benzodiazepine receptor
radioisotope
animal cell
central nervous system
circadian rhythm
drug accumulation
drug receptor binding
endocrine system
flunitrazepam h 3
nonhuman
pharmacokinetics
pineal body
rat
superior cervical ganglionectomy
Animal
Biological Transport
Cerebral Cortex
Female
Flunitrazepam
Kinetics
Organ Specificity
Pineal Gland
Rats
Rats, Inbred Strains
Receptors, GABA-A
Support, Non-U.S. Gov't
Lowenstein, P.R.
Solveyra, C.G.
Cardinali, D.P.
In Vitro Uptake of Benzodiazepines by Rat Pineal Gland
topic_facet benzodiazepine uptake
diurnal rhythms
pineal gland
superior cervical ganglionectomy
benzodiazepine
benzodiazepine receptor
radioisotope
animal cell
central nervous system
circadian rhythm
drug accumulation
drug receptor binding
endocrine system
flunitrazepam h 3
nonhuman
pharmacokinetics
pineal body
rat
superior cervical ganglionectomy
Animal
Biological Transport
Cerebral Cortex
Female
Flunitrazepam
Kinetics
Organ Specificity
Pineal Gland
Rats
Rats, Inbred Strains
Receptors, GABA-A
Support, Non-U.S. Gov't
description 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 3H‐flunitrazepam (FNZP) by rat pineal glands in vitro. At 37 °C, 3H‐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 Km's of 1.74 and 1.45 μM, and Vmax'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 3H‐FNZP uptake. Cerebral cortex explants of similar size and weight as the pineal ones took up 3H‐FNZP to a maximum tissue/ medium concentration of about 2. Neither pineal nor cerebral cortex 3H‐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 3H‐FNZP uptake significantly. Other tissues, such as liver, muscle, kidney, adrenal gland, or anterior pituitary, took up 3H‐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. Copyright © 1984, Wiley Blackwell. All rights reserved
format JOUR
author Lowenstein, P.R.
Solveyra, C.G.
Cardinali, D.P.
author_facet Lowenstein, P.R.
Solveyra, C.G.
Cardinali, D.P.
author_sort Lowenstein, P.R.
title In Vitro Uptake of Benzodiazepines by Rat Pineal Gland
title_short In Vitro Uptake of Benzodiazepines by Rat Pineal Gland
title_full In Vitro Uptake of Benzodiazepines by Rat Pineal Gland
title_fullStr In Vitro Uptake of Benzodiazepines by Rat Pineal Gland
title_full_unstemmed In Vitro Uptake of Benzodiazepines by Rat Pineal Gland
title_sort in vitro uptake of benzodiazepines by rat pineal gland
url http://hdl.handle.net/20.500.12110/paper_07423098_v1_n3_p207_Lowenstein
work_keys_str_mv AT lowensteinpr invitrouptakeofbenzodiazepinesbyratpinealgland
AT solveyracg invitrouptakeofbenzodiazepinesbyratpinealgland
AT cardinalidp invitrouptakeofbenzodiazepinesbyratpinealgland
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