Effect of experimental diabetes on cholinergic, purinergic and peptidergic motor responses of the isolated rat bladder to electrical field stimulation or capsaicin

Background: A report examining whether clinically available antidepressants increase urethral smooth muscle contraction via antagonistic effects on the α2-adrenoceptor (α2-AR) is lacking. Objectives: The present study was performed to evaluate the potential of clinically available antidepressants to reverse α2-AR-mediated contractile inhibition in rat vas deferens, in order to predict whether they can induce voiding impairment. Method: The effects of 18 antidepressants of different classes on electrical field stimulation (EFS)-induced contractions suppressed by 10–8 mol/L clonidine (a selective α2-AR agonist) in isolated rat vas deferens were investigated and related to their respective clinical blood concentrations. Results: The EFS-induced contractions suppressed by clonidine were recovered by amitriptyline (a tricyclic antidepressant), mirtazapine (a noradrenergic and specific serotonergic antidepressant), and trazodone (a serotonin 5-HT2A receptor antagonist) at concentrations close to the clinical blood levels. EFS-induced contractions were also recovered by trimipramine, clomipramine (tricyclic antidepressants), mianserin (a tetracyclic antidepressant), sertraline (a selective serotonin reuptake inhibitor [SSRI]), and sulpiride (a dopamine D2-receptor antagonist), albeit at concentrations that substantially exceeded their clinically-achievable blood levels. EFS-induced contractions were not significantly affected by imipramine, nortriptyline, amoxapine (tricyclic antidepressants), maprotiline (a tetracyclic antidepressant), fluvoxamine, paroxetine, escitalopram (SSRIs), milnacipran, duloxetine (serotonin and noradrenaline reuptake inhibitors), and aripiprazole (a dopamine partial agonist). Conclusions: These findings suggest that amitriptyline, mirtazapine, and trazodone induce voiding impairment caused by increased urethral resistance by enhancing sympathetic nerve activities attributed to α2-AR antagonism.

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The effect of fluoxetine on electrical field stimulation-induced responses in the isolated rat small intestine

Methods and Findings in Experimental and Clinical Pharmacology ◽

10.1358/mf.2010.32.9.1543307 ◽

2010 ◽

Vol 32 (9) ◽

pp. 645 ◽

Cited By ~ 1

Author(s):

F. Farajian-Mashradi ◽

R.J. Naylor ◽

F.A. Javid

Keyword(s):

Small Intestine ◽

Electrical Field Stimulation ◽

Induced Responses ◽

Field Stimulation ◽

Rat Small Intestine ◽

Electrical Field ◽

Isolated Rat

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Hydrogen peroxide-induced potentiation of contractile responses in isolated rat airways

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1990.258.4.l232 ◽

1990 ◽

Vol 258 (4) ◽

pp. L232-L237 ◽

Cited By ~ 6

Author(s):

J. L. Szarek ◽

N. L. Schmidt

Keyword(s):

Hydrogen Peroxide ◽

Smooth Muscle ◽

Electrical Stimulation ◽

Airway Smooth Muscle ◽

Electrical Field Stimulation ◽

Airway Hyperreactivity ◽

Field Stimulation ◽

Electrical Field ◽

Contractile Responses ◽

Isolated Rat

We hypothesized that metabolites of O2 may play a role in the development of airway hyperreactivity and undertook this study to examine the effects of one of these metabolites, hydrogen peroxide (H2O2), on electrical field stimulation-induced contractile responses of isolated rat intrapulmonary bronchi. Exposure to H2O2 (1 mM) elicited a transient contractile response with a peak response equivalent to 18.1 +/- 2.0% of the reference contraction obtained to electrical stimulation. The H2O2-induced contraction was attenuated by pretreatment of tissues with indomethacin and superoxide dismutase, but abolished by catalase and mianserin. Subsequent to H2O2 exposure, electrical field stimulation-induced contractile responses were potentiated (P less than 0.0001), whereas acetylcholine-induced contractions were not. The potentiating effects of H2O2 were inhibited by catalase and mianserin. Addition of 5-hydroxytryptamine (5-HT) to the bath similarly potentiated contractions to electrical stimulation (P less than 0.0001). Together, these results are consistent with a role for 5-HT in H2O2-induced contraction and the subsequent potentiation of airway smooth muscle contraction elicited by cholinergic nerve activation. Thus endogenous metabolites of O2 may be important in modulating airway smooth muscle tone.

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