Altered levels of mRNA expression and pharmacological reactivity of alpha1-adrenergic receptor subtypes in the late-pregnant rat myometrium.
The adrenergic system plays a major role in the regulation of the uterine contractility during pregnancy. Our previous studies have shown the significance of the alpha1-adrenergic receptors (ARs) in the control of pregnant uterine contractility both in vitro and in vivo. Our present aim was to determine the changes in mRNA expression and pharmacological reactivity of the alpha1-ARs on days 18, 20, and 22 of pregnancy. To demonstrate the expressions of alpha1-AR subtype mRNA, we used a reverse transcription-polymerase chain reaction (RT-PCR); the pharmacological reactivity was tested by electric field stimulation (EFS). The expression of alpha1A-AR mRNA increased from day 18 to 22, while no alpha1B-AR mRNA was detectable. We found a small increase in the expression of alpha1D-AR mRNA on day 20, which was not followed by a significant change in pharmacological reactivity. The alpha1D-receptor expression and pharmacological reactivity decreased significantly up to day 22. EFS studies revealed that the alpha1A-AR antagonist 5-methylurapidil had EC50 values (1.9 x 10(-6)-6.3 x 10(-6) M) about one order of magnitude lower than those of the alpha1D-AR antagonist BMY 7378 (4 x 10(-6)-3.6 x 10(-5) M). However, the alpha1B-AR antagonist cyclazosine exerted only a slight effect on the stimulated contractions. Strong correlations were found between the alpha1A-mRNA expression and the EC50 of 5-methylurapidil (r(2) =0.9712), and between the alpha1D-AR mRNA expression and the EC50 of BMY 7378 (r(2) = 0.9937). Our findings suggest that both alpha1A- and alpha1D-ARs are involved in the regulation of the pregnant uterine contractility. The density and pharmacological reactivity indicate that the alpha(1A)-AR seems to play the major role in late-pregnant myometrial contraction.
Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
Eszter
E
Ducza
Róbert
R
Gáspár
George
G
Falkay
D000818:Animals; D003496:Cyclazocine / Q000494:pharmacology; D004599:Electric Stimulation Therapy; D005260:Female; D008297:Male; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010879:Piperazines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D003496:Cyclazocine; C053428:BMY 7378