![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
BB Wolfe, TK Harden, JR Sporn and PB Molinoff
Treatment with desmethylimipramine (DMI), a tricyclic antidepressant, for 7 to 21 days resulted in a 35 to 45% decrease in the accumulation of adenosine cyclic 3':5'-monophosphate (cAMP) in response to a maximally effective concentration of (-)-isoproterenol (ISO) in rat cerebral cortical slices. The EC50 for ISO-stimulated cAMP accumulation was not affected by DMI administration. The diminution in responsiveness to catecholamines was accompanied by a 35 to 40% decrease in the density of beta adrenergic receptors as measured by the binding of [125I]iodohydroxybenzylpindolol. Decreases in ISO-sensitive cAMP accumulation and in beta adrenergic receptor density were temporally correlated, maximal decreases being observed within 5 to 7 days. Within 7 days after cessation of chronic DMI treatment ISO- stimulated cAMP accumulation and beta adrenergic receptor density returned to normal. The role of presynaptic nerve terminals in mediating these phenomena was also investigated. Treatment of newborn rats with 6--hydroxydopamine inhibited the development of noradrenergic nerve terminals in the cerebral cortex and blocked the effects of DMI on cortical cAMP accumulation and on beta adrenergic receptor density. The administration of the beta adrenergic receptor antagonist propranolol led to increases in maximal ISO-stimulated cAMP accumulations and beta adrenergic receptor density in the rat cerebral cortex. This increase was not affected by the simultaneous administration of propranolol and DMI. Thus, the effect of DMI appears to be mediated through an action of norepinephrine at beta adrenergic receptors. Chronic treatment with two other clinically effective antidepressants, pargyline and iprindole, led to effects similar to those observed with DMI administration. Pretreatment of neonates with 6- hydroxydopamine blocked the effect of iprindole on beta adrenergic receptors. Preincubation of cortical membranes with guanosinetriphosphate before determination of the density of beta adrenergic receptors had no effect on the decreased number of receptors had no effect on the decreased number of receptors seen in DMI-treated animals. These experiments suggest that antidepressants, acting presynaptically, increase the concentration of transmitter at noradrenergic synapses and induce a compensatory decrease in the density of beta adrenergic receptors.
This article has been cited by other articles:
|
|
 |
|
  S. Avissar, A. Matuzany-Ruban, K. Tzukert, and G. Schreiber {beta}-Arrestin-1 Levels: Reduced in Leukocytes of Patients With Depression and Elevated by Antidepressants in Rat Brain Am J Psychiatry, November 1, 2004; 161(11): 2066 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Burgi, K. Baltensperger, and U. E. Honegger Antidepressant-induced Switch of beta 1-Adrenoceptor Trafficking as a Mechanism for Drug Action J. Biol. Chem., January 3, 2003; 278(2): 1044 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Linder and P. E. Keck Jr. Standards of laboratory practice: antidepressant drug monitoring Clin. Chem., May 1, 1998; 44(5): 1073 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Russo-Neustadt and C. W. Cotman Adrenergic Receptors in Alzheimer's Disease Brain: Selective Increases in the Cerebella of Aggressive Patients J. Neurosci., July 15, 1997; 17(14): 5573 - 5580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.F. Martin, I. Phillips, D.J. Heal, and W.R. Buckett Antidepressant treatments, including electroconvulsive shock and the putative antidepressant sibutramine hydrochloride, do not alter [3H]-prazosin binding to rat cortical membranes J Psychopharmacol, January 1, 1989; 3(2): 70 - 75. [Abstract] [PDF]
|
|
|
|
 |
|
 P. G. Weiler, D. Mungas, and C. Bernick Propranolol for the Control of Disruptive Behavior in Senile Dementia J Geriatr Psychiatry Neurol, October 1, 1988; 1(4): 226 - 230. [PDF]
|
|
|
|
 |
|
 C. Stockmeier, A. Martino, and K. Kellar A strong influence of serotonin axons on beta-adrenergic receptors in rat brain Science, October 18, 1985; 230(4723): 323 - 325. [Abstract] [PDF]
|
|
|
|
|
|
B. Perry, J. Stolk, G Vantini, R. Guchhait, and D. U'Prichard Strain differences in rat brain epinephrine synthesis: regulation of alpha-adrenergic receptor number by epinephrine Science, September 23, 1983; 221(4617): 1297 - 1299. [Abstract] [PDF]
|
|
|
|
|
|
C. Lee, J. Javitch, and S. Snyder Recognition sites for norepinephrine uptake: regulation by neurotransmitter Science, May 6, 1983; 220(4597): 626 - 629. [Abstract] [PDF]
|
|
|
|
|
|
D. Menkes, M. Rasenick, M. Wheeler, and M. Bitensky Guanosine triphosphate activation of brain adenylate cyclase: enhancement by long-term antidepressant treatment Science, January 7, 1983; 219(4580): 65 - 67. [Abstract] [PDF]
|
|
|
|
|
|
A Janowsky, F Okada, D. Manier, C. Applegate, F Sulser, and L. Steranka Role of serotonergic input in the regulation of the beta-adrenergic receptor-coupled adenylate cyclase system Science, November 26, 1982; 218(4575): 900 - 901. [Abstract] [PDF]
|
|
|
|
|
|
S. Peroutka and S. Snyder Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding Science, October 3, 1980; 210(4465): 88 - 90. [Abstract] [PDF]
|
|
|
|
|
|
K. Minneman, M. Dibner, B. Wolfe, and P. Molinoff beta1- and beta2-Adrenergic receptors in rat cerebral cortex are independently regulated Science, May 25, 1979; 204(4395): 866 - 868. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
