Muscle layer- and region-dependent distributions of oxytocin receptors in the porcine myometrium.
The aim of the present study was to clarify smooth muscle- and region-dependent distributions of the oxytocin receptor that mediates oxytocin-induced contraction in the nonpregnant porcine myometrium by means of mechanical and radioligand ([3H]-oxytocin) binding studies. In Krebs solution, oxytocin (0.1-300 nM) caused concentration-dependent contractions of the cornual myometrium, and the longitudinal muscle was more sensitive than the circular muscle. [Arg8]-vasopressin and [deamino-Cys1, D-Arg8]-vasopressin also contracted the myometrium, and the order of the potency was oxytocin > [Arg8]-vasopressin > [deamino-Cys(1), D-Arg(8)]-vasopressin. Treatment with a high concentration of oxytocin selectively inhibited the contraction of oxytocin and [Arg8]-vasopressin without affecting the responses of acetylcholine and high-K+. Selective cross inhibition was also observed in the presence of a high concentration of [Arg(8)]-vasopressin. The oxytocin-induced contraction was resistant to tetrodotoxin and atropine, but was reduced by verapamil or by the removal of external Ca2+, indicating that oxytocin has a direct action on smooth muscle cells and that extracellular Ca2+ plays an important role for the contraction. In Kumagai solution, oxytocin caused contraction of the cornual longitudinal muscle (-logEC50 = 8.5) but not the circular muscle. Longitudinal muscles of other regions (corpus and cervix) were also responsive to oxytocin, but the -logEC50 value differed from region to region (cornua > corpus = cervix). On the other hand, oxytocin failed to cause contraction of the corpus and cervical circular muscles. 3H-Oxytocin bound to crude membrane preparations of the myometrium in a concentration-dependent (0.084-2.7 nM) saturable manner. Scatchard analysis of equilibrium binding data revealed the presence of a single class of binding site with an apparent dissociation constant (Kd, 1.1-1.5 nM), but receptor density (Bmax) differed in the two muscle layer types (longitudinal muscle: circular muscle = 5:1) and tended to decrease from the cornua to the cervix. In conclusion, the receptor specific for oxytocin is present in the porcine myometrium and mediates the contractile responses of both oxytocin and [Arg8]-vasopressin. The distribution of the oxytocin receptors differs according to the type of muscle layer (longitudinal muscle > circular muscle) and the region of the uterus.
Kitazawa
T
T
Department of Pharmacology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, 069-8501, Hokkaido, Japan.
Kajiwara
T
T
Kiuchi
A
A
Hatakeyama
H
H
Taneike
T
T
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D018045:Receptors, Oxytocin / Q000096:biosynthesis*; D013552:Swine; D014018:Tissue Distribution
D018045:Receptors, Oxytocin; D001127:Arginine Vasopressin; D010121:Oxytocin; D011188:Potassium