Binding of four oxytocin analogues to myometrial oxytocin and arginine-vasopressin binding sites in pregnant women.
The binding of 3H-oxytocin (3H-OT) and 3H-arginine-vasopressin (3H-AVP) and the displacement from binding sites by four oxytocin analogues were studied in myometrial membrane preparations from full-term pregnant women. Specific 3H-OT binding was saturable with a maximal binding capacity of 76.1 fmol/mg DNA, and a dissociation constant of 0.5 pM. Corresponding values regarding 3H-AVP was 148.6 fmol/mg DNA and 0.7 pM. The oxytocin analogues tested demonstrated a high specific binding to the OT and AVP receptor sites; in fact, the affinity of the analogues to the 3H-AVP binding sites was higher than to the 3H-OT binding sites. The order of potency between the analogues was CAU greater than CAM greater than CAP greater than CAO and CAP greater than CAU greater than CAO greater than CAM for the OT and AVP binding sites, respectively. The displacement of oxytocin and arginine-vasopressin, respectively, from the myometrial receptor sites indicate partly separate binding sites for oxytocin and AVP and might implicate that AVP can be of importance in regulating myometrial activity in pregnancy. The results on oxytocin analogues imply that other pharmacological tests must be performed for quantification of the relaxing effects on the uterus and to determine the optimal analogue for clinical trials in preterm labor and dysmenorrhoea.
Rydén
G
G
Department of Obstetrics and Gynecology, Faculty of Health Sciences, Linköping, Sweden.
Andersson
R G
RG
Berg
G
G
Karlsson
S G
SG
Oscarsson
Y
Y
D001127:Arginine Vasopressin / Q000378:metabolism*; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000378:metabolism*; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism; D018045:Receptors, Oxytocin; D015145:Tocolysis / Q000379:methods
D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D001127:Arginine Vasopressin; D010121:Oxytocin