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-depen dent distributions of the oxytocin receptor that mediates oxytocin-induced contraction in the nonpregnant porcine myometrium by means of mechanical an d radioligand ([H-3]-oxytocin) binding studies. In Krebs solution, oxytocin (0.1-300 nM) caused concentration-dependent contractions of the cornual my ometrium, and the longitudinal muscle was more sensitive than the circular muscle. [Arg(8)]-vasopressin and [deamino-Cys(1), D-Arg(8)]-vasopressin als o contracted the myometrium, and the order of the potency was oxytocin > [A rg(8)]-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 acetylch oline and high-K+ Selective cross inhibition was also observed in the prese nce of a high concentration of [Arg8]-vasopressin. The oxytocin-induced con traction was resistant to tetrodotoxin and atropine, but was reduced by ver apamil or by the removal of external Ca2+, indicating that oxytocin has a d irect action on smooth muscle cells and that extracellular Ca2+ plays an im portant role for the contraction. In Kumagai solution, oxytocin caused cont raction of the cornual longitudinal muscle (-logEC(50) = 8.5) but not the c ircular muscle. Longitudinal muscles of other regions (corpus and cervix) w ere also responsive to oxytocin, but the -logEC(50) value differed from reg ion to region (cornua > corpus = cervix). On the other hand, oxytocin faile d to cause contraction of the corpus and cervical circular muscles. H-3-Oxy tocin bound to crude membrane preparations of the myometrium in a concentra tion-dependent (0.084-2.7 nM) saturable manner. Scatchard analysis of equil ibrium 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 dens ity (Bmax) differed in the two muscle layer types (longitudinal muscle: cir cular muscle = 5:1) and tended to decrease from the cornua to the cervix. I n conclusion, the receptor specific for oxytocin is present in the porcine myometrium and mediates the contractile responses of both oxytocin and [Arg (8)]-vasopressin. The distribution of the oxytocin receptors differs accord ing to the type of muscle layer (longitudinal muscle > circular muscle) and the region of the uterus. (C) 2001 Elsevier Science Inc. All rights reserv ed.