TY - JOUR
T1 - Opposite effects of acute and repeated administration of desmethylimipramine on adrenergic responsiveness in rat pineal gland
AU - Moyer, John A.
AU - Greenberg, Louise H.
AU - Frazer, Alan
AU - Brunswick, David J.
AU - Mendels, Joe
AU - Weiss, Benjamin
N1 - Funding Information:
This work was supported by NIMH grants MH-14654, MH-29094, MH-27289, and MH-30096 and research funds from the Veterans Administration .
PY - 1979/6/11
Y1 - 1979/6/11
N2 - 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.
AB - 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.
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U2 - 10.1016/0024-3205(79)90100-0
DO - 10.1016/0024-3205(79)90100-0
M3 - Article
C2 - 228145
AN - SCOPUS:0018664772
SN - 0024-3205
VL - 24
SP - 2237
EP - 2244
JO - Life Sciences
JF - Life Sciences
IS - 24
ER -