Oxytocic activity of thrombin: modulation of thrombin-induced gravid rat myometrial contractions by 5-hydroxytryptamine receptor antagonists.
BACKGROUND
Thrombin possesses potent oxytocic activity in vitro and in vivo. This activity has been proposed to play a role in post-parturitional uterine contractions and possibly, preterm birth related to intrauterine hemorrhage. Previous workers have demonstrated that cyclo-oxygenase pathway may not play a significant role in oxytocic activity of thrombin. However, the role of 5-hydroxytryptamine (a mediator of some of the biological activities of thrombin) in the oxytocic activity of thrombin is unknown. The present study therefore aimed to examine the possible involvement of 5-hydroxytryptamine in thrombin-induced myometrial contractions.


METHODS
Effect of 5-hydroxytryptamine receptor antagonists on thrombin-induced contractions of isolated gravid rat myometrium was studied using isolated tissue bath system.


RESULTS
Thrombin-induced myometrial contractions were significantly and concentration-dependently inhibited by ketanserin and methysergide. Furthermore, 12 +/- 2% increase in the force of contractions of gravid rat myometrium pre-contracted with 5-hydroxytryptamine (1 microM) was provoked by 1 U/ml of thrombin. Thrombin-induced augmentation of the uterine stimulating effect of 5-hydroxytryptamine was characterized by pronounced increase in the contractile tone.


CONCLUSIONS
5-hydroxytryptamine may possibly play a role in oxytocic activity of thrombin. Uterine hyperactivity associated with intrauterine hemorrhage could hence involve thrombin-induced 5-hydroxytryptamine production in the uterus.
Adebiyi
Adebowale
A
Department of Obstetrics and Gynecology, National University of Singapore, National University Hospital, Singapore.
Adaikan
Ganesan P
GP
Prasad
Rama N V
RN
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects*; D010120:Oxytocics / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013917:Thrombin / Q000008:administration & dosage / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D010120:Oxytocics; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D013917:Thrombin; D008784:Methysergide