Evaluating the role of the serotoninergic system in the control of human seminal vesicle smooth muscle-an in vitro approach.
BACKGROUND
It has been suggested that serotonin re-uptake inhibitors (SRIs) may retard the ejaculatory response by acting directly on the seminal vesicle (SV) and ductus deferens smooth muscle. However, until now, only a very few experimental studies have investigated such potential local (peripheral) effects.


OBJECTIVE
To elucidate the effects of serotonin (5-HT) and the SRIs clomipramine, fluoxetine and imipramine on the tension induced by norepinephrine (NE) of isolated human SV smooth muscle, as well as on the production of tissue cyclic AMP and cyclic GMP.


METHODS
To measure the inhibition exerted by serotonin and SRIs clomipramine, fluoxetine, and imipramine on the contractile response of isolated SV tissue. In addition, the effects of the drugs on the turn-over of cyclic nucleotides cAMP and cGMP were also elucidated.


METHODS
The effects of the cumulative addition of serotonin and the SRIs clomipramine, fluoxetine and imipramine (1 nM-10 microM) on the tension induced by the alpha(1)-adrenoceptor agonist NE (10 microM) of SV strip preparations were studied using the organ bath technique. Cyclic AMP and cyclic GMP were measured by means of specific radioimmunoassays.


RESULTS
The tension induced by NE was dose-dependently reversed by the drugs tested. The rank order of efficacy was: imipramine > or = fluoxetine > or = clomipramine > serotonin. Mean reversion of tension was measured between 66 +/- 6.6% and 52 +/- 6.6%. These effects were paralleled by a 1.3-fold to 2.7-fold increase in tissue cAMP in response to exposure to the drugs. In contrast, no significant enhancement in cGMP was noted.


CONCLUSIONS
The findings, for the first time, present evidence that SRIs may antagonize the sympathetic contraction of SV smooth muscle via stimulation of tissue cyclic AMP.
Birowo
Ponco
P
Department of Urology & Uro-Oncology, Hannover Medical School, Hannover 30625, Germany.
Uckert
Stefan
S
Kedia
George T
GT
Scheller
Friedemann
F
Meyer
Markus
M
Taher
Akmal
A
Rahardjo
Djoko
D
Jonas
Udo
U
Kuczyk
Markus A
MA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000368:Aged; D002997:Clomipramine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004542:Ejaculation / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D012669:Seminal Vesicles / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012735:Sexual Dysfunction, Physiological; D014649:Vas Deferens / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D002997:Clomipramine; D000242:Cyclic AMP; D006152:Cyclic GMP; D005473:Fluoxetine; D007099:Imipramine; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors