The roles of alpha2-adrenoceptor subtypes in the control of cervical resistance in the late-pregnant rat.
The roles of the alpha(2)-adrenoceptor subtypes in the regulation of cervical resistance have previously not been investigated. The aim of the present study was to identify these receptors in the late-pregnant cervix and determine their functions in vitro in the rat. The expressions of the alpha(2)-adrenoceptor subtypes were determined by means of RT-PCR and Western blotting techniques. The changes in cervical resistance due to subtype-selective antagonists were investigated in stretching tests. The cyclic AMP immunoassay technique was used to detect the level of cyclic AMP following stimulation of the alpha(2)-adrenoceptors with or without pertussis toxin. On pregnancy days 18, 20, 21 and 22, the RT-PCR and Western blotting studies revealed the expressions of all three alpha(2)-adrenoceptor subtype mRNAs and proteins. On days 18 and 20, noradrenaline increased and decreased the resistance, respectively. Its effect was blocked by each of the antagonists used, except ARC 239 on both days. On day 21, noradrenaline again increased the resistance, this effect being maintained only in the presence of spiroxatrine. Noradrenaline was ineffective on day 22. These results were supported by the changes in cyclic AMP levels. Pertussis toxin pretreatment eliminated the changes in the cyclic AMP level on days 18 and 21. We presume that the alpha(2A)- and alpha(2C)-adrenoceptors play predominant roles in the regulation of cervical resistance on days 18-21. Depending on the day of pregnancy, stimulation of these alpha(2)-adrenoceptors could even result in opposite effects. This fluctuation can be explained by the changes in the G(i)/G(s)-coupling of the alpha(2A)- and alpha(2C)-adrenoceptors.
Gál
Adrienn
A
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary. adrienngal@pharm.u-szeged.hu
Ducza
Eszter
E
Minorics
Renáta
R
Klukovits
Anna
A
Gálik
Márta
M
Falkay
George
G
Gáspár
Róbert
R
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D015153:Blotting, Western; D020070:Cervical Ripening / Q000187:drug effects* / Q000502:physiology; D002584:Cervix Uteri / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013141:Spiro Compounds / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
C547770:Adra2a protein, rat; C547776:Adra2c protein, rat; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D004146:Dioxanes; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D013141:Spiro Compounds; C018387:spiroxatrine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; C032994:AR-C239; D009638:Norepinephrine