[The effect of the ARC 239 on the myometrial and cervical action in the rat, in vitro].
The premature labour is one of the major challenges in the clinical practice. Finding new agents and mechanisms in the control of uterine activity is the main objective of the last decade's experiments. One of the new targets is the alpha2-adrenoceptors (alpha2-AR). The purpose of this study was to determine the effect of the alpha2B/C-adrenoceptor blocker ARC 239 on the myometrial contractions and the cervical resistance on pregnant rats, in vitro. We identified the alpha2-adrenoceptor subtypes proteins both in the myometrial and the cervical samples. In isolated organ studies, the ARC 239 exerted a strong inhibitory effect on noradrenaline-stimulated contractions. The effect of ARC 239 on labour-induced myometrial samples was also convincing. In the stretching test, the cervical resistance was increased and decreased in by ARC 239 on pregnancy days 18 and 20, respectively. ARC 239 did not have effect on the 22-day pregnant cervical samples. These results were supported by the cAMP studies. We can conclude that, the alpha2B-adrenoceptors predominate and mediate contraction, while the alpha2A- and alpha2C-ARs decrease the contractile response to noradrenaline in 22-days-pregnant animals. In the pregnant cervix the alpha2-adrenoceptors can couple to both G(i)- and G()-proteins in the 18- and 20-day-pregnant samples, respectively, resulting in increase or decrease in the cervical resistance. Based on these facts we suggest that ARC 239 may open new perspective in the influence of premature labour.
Gál
Adrienn
A
Szegedi Tudományegyetem Gyógyszerésztudományi Kar, Gyógyszerhatástani és Biofarmáciai Intézet, Szeged.
Kolarovszki-Sipiczki
Zoltán
Z
Gálik
Márta
M
Ducza
Eszter
E
Minorics
Renáta
R
Klukovits
Anna
A
Falkay
György
G
Gáspár
Róbert
R
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002584:Cervix Uteri / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D007546:Isoquinolines; D010879:Piperazines; C032994:AR-C239