Cyclic AMP Second-Messenger Signal Amplification in Depression

1988 ◽  
Vol 152 (5) ◽  
pp. 665-669 ◽  
Author(s):  
Richard P. Ebstein ◽  
Bernard Lerer ◽  
Baruch Shapira ◽  
Zecharia Shemesh ◽  
Daniel G. Moscovich ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Signal Amplification ◽  
Antidepressant Treatment ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Late Night ◽  
Depressed Patients ◽  
Cyclic Amp Accumulation ◽  
Significant Clinical Improvement ◽  
Age And Sex

Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.

The relationship between some beta-adrenergic mediated responses and plasma concentrations of adrenaline and cyclic AMP in man

1990 ◽  
Vol 122 (1) ◽  
pp. 115-120 ◽  
Author(s):  
E. K. Philipsen ◽  
J. Myhre ◽  
S. Larsen ◽  
M. Damkjær Nielsen ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Plasma Concentrations ◽  
Beta Agonist ◽  
Beta Blockade ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Plasma Adrenaline ◽  
Beta Adrenoceptor ◽  
Adrenaline Infusion ◽  
The Relationship

Abstract To test the hypothesis that increments in plasma cyclic AMP during beta-adrenergic stimulation reflect integrated second messenger function of the tissues activated by the angonist, graded adrenaline infusion resulting in plasma adrenaline concentrations within the physiological range was performed in 8 healthy subjects with and without concomitant beta-adrenoceptor blockade by iv propranolol. A significant correlation was found between increments in plasma adrenaline and plasma cyclic AMP in the experiments without beta-blockade; during concomitant beta-blockade the increase in plasma cyclic AMP concentrations at low adrenaline infusion rates was prevented, whereas a small increase in cyclic AMP was found at high adrenaline infusion rates, probably owing to incomplete beta-receptor blockade. Likewise, the adrenaline-induced increments in blood substrates (glucose, lactate, glycerol and betahydroxy butyric acid) were significantly reduced but not completely prevented by beta-blockade. We conclude that an altered relationship between beta-agonist concentrations and plasma cyclic AMP may provide evidence for the existence of differences in beta-adrenergic sensitivity in man.

scholarly journals On the mechanism of the reduction by thyroid hormone of β-adrenergic relaxation rate stimulation in rat heart

1989 ◽  
Vol 259 (1) ◽  
pp. 229-236 ◽  
Author(s):  
R E Beekman ◽  
C van Hardeveld ◽  
W S Simonides
Keyword(s):  
Thyroid Hormone ◽  
Protein Kinase ◽  
Sarcoplasmic Reticulum ◽  
Cyclic Amp ◽  
Relaxation Rate ◽  
Cardiac Tissue ◽  
Fold Increase ◽  
Protein Kinase Activity ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic

The effects of beta-adrenergic stimulation on the relaxation rate and the Ca2+-transport rate in sarcoplasmic reticulum of hypothyroid, euthyroid and hyperthyroid rat hearts were studied. Administration of isoproterenol (0.1 microM) to perfused, electrically stimulated hearts (5 Hz) caused a decrease in the half-time of relaxation (RT 1/2) the extent of which depended on the thyroid status, i.e. hypothyroid (-24%), euthyroid (-19%) or hyperthyroid (-8%). A similar decreasing effect was found for the stimulation of Ca2+ transport in isolated SR by cyclic AMP and protein kinase, i.e. hypothyroid (75%), euthyroid (37%) and hyperthyroid (20%). These alterations were not due to differences in endogenous protein kinase activity or cyclic AMP production. Estimations of Ca2+-ATPase and phospholamban (PL) content of the sarcoplasmic reticulum were obtained by measurement of the phosphorylated forms of Ca2+-ATPase (E-P) and phospholamban (PL-P) followed by electrophoresis and autoradiography. A 3-fold decrease of PL-P, accompanied by a 2-fold increase of E-P per mg of protein was observed in sarcoplasmic reticulum preparations in the direction hypothyroid----hyperthyroid. Consequently the E-P/PL-P ratio increased from 0.32 (hypothyroid), through 0.81 (euthyroid) to 1.69 (hyperthyroid). In spite of certain limitations inherent to quantification of Ca2+-ATPase and phospholamban by their phosphorylated products, these data provide strong evidence that during thyroid-hormone mediated cardiac hypertrophy, with concomitant proliferation of the sarcoplasmic reticulum, the relative amount of phospholamban decreases with respect to Ca2+-ATPase. This could provide an explanation for the observed gradual diminishment of the beta-adrenergic effect on the relaxation rate when cardiac tissue is exposed to increasing amounts of thyroid hormone.

Beta-adrenergic stimulation of cyclic AMP production in the rabbit urinary bladder

1986 ◽  
Vol 5 (2) ◽  
pp. 227-233 ◽  
Author(s):  
Robert M. Levin ◽  
Michael R. Ruggieri ◽  
Joseph Hypolite ◽  
Alan J. Wein
Keyword(s):  
Urinary Bladder ◽  
Cyclic Amp ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Rabbit Urinary Bladder ◽  
Stimulation Of
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