Opposite effects of acute and repeated administration of desmethylimipramine on adrenergic responsiveness in rat pineal gland

John A. Moyer, Louise H. Greenberg, Alan Frazer, David J. Brunswick, Joe Mendels, Benjamin Weiss

Research output: Contribution to journalArticle

33 Scopus citations

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 in vivo. 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.

Original languageEnglish (US)
Pages (from-to)2237-2244
Number of pages8
JournalLife Sciences
Volume24
Issue number24
DOIs
StatePublished - Jun 11 1979
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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