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Opposite effects of acute and repeated administration of desmethylimipramine on adrenergic responsiveness in rat pineal gland.
Authors:J A Moyer  L H Greenberg  A Frazer  D J Brunswick  J Mendels  B Weiss
Institution:1. Affective Diseases Research Unit, Veterans Administration Hospital and Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pa. 19104, USA;2. Department of Pharmacology, Medical College of Pennsylvania, Philadelphia, Pa. 19129, USA
Abstract:The effect of acute and repeated desmethylimipramine (DMI) treatment on catecholamine-stimulated production of adenosine 3', 5'-monophosphate (cyclic AMP) in rat pineal gland was studied invivo. In rats exposed to continuous illumination, the administration of isoproterenol (2μmol/kg) to control animals produced a marked increase in the concentration of cyclic AMP in pineal gland. In contrast, norepinephrine (2μmol/kg) failed to increase the levels of cyclic AMP. After acute treatment with DMI (single injection, 38μmol/kg, i. p.), the isoproterenol-induced rise in cyclic AMP was not significantly different from that measured in control animals. However, acute DMI treatment did allow a significant elevation in the concentration of cyclic AMP in pineal gland in response to norepinephrine. In rats given nine injections of DMI (38μmol/kg, i.p., twice daily) neither isoproterenol nor norepinephrine caused a significant increase in the concentration of cyclic AMP in pineal glands. Although acute treatment with DMI had no significant effect on 3H] dihydroalprenolol binding, chronic treatment with DMI significantly reduced 3H] dihydroalprenolol binding in the pineal gland. The results of this study suggest that while a single administration of DMI can enhance adrenergic responses elicited by norepinephrine, chronic administration of DMI leads to compensatory decreases in receptor density and adrenergic responsiveness.
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