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Pharmacologic characterization of the oxytocin receptor in human uterine smooth muscle cells.

Abstract
[(3)H]-oxytocin was used to characterize the oxytocin receptor found in human uterine smooth muscle cells (USMC). Specific binding of [(3)H]-oxytocin to USMC plasma membranes was dependent upon time, temperature and membrane protein concentration. Scatchard plot analysis of equilibrium binding data revealed the existence of a single class of high-affinity binding sites with an apparent equilibrium dissociation constant (K(d)) of 0.76 nM and a maximum receptor density (B(max)) of 153 fmol mg(-1) protein. The Hill coefficient (n(H)) did not differ significantly from unity, suggesting binding to homogenous, non-interacting receptor populations. Competitive inhibition of [(3)H]-oxytocin binding showed that oxytocin and vasopressin (AVP) receptor agonists and antagonists displaced [(3)H]-oxytocin in a concentration-dependent manner. The order of potencies for peptide agonists and antagonists was: oxytocin>[Asu(1,6)]-oxytocin>AVP= atosiban>d(CH(2))(5)Tyr(Me)AVP>[Thr(4),Gly(7)]-oxytocin>dDAVP, and for nonpeptide antagonists was: L-371257>YM087>SR 49059>OPC-21268>SR 121463A>OPC-31260. Oxytocin significantly induced concentration-dependent increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) and hyperplasia in USMC. The oxytocin receptor antagonists, atosiban and L-371257, potently and concentration-dependently inhibited oxytocin-induced [Ca(2+)](i) increase and hyperplasia. In contrast, the V(1A) receptor selective antagonist, SR 49059, and the V(2) receptor selective antagonist, SR 121463A, did not potently inhibit oxytocin-induced [Ca(2+)](i) increase and hyperplasia. The potency order of antagonists in inhibiting oxytocin-induced [Ca(2+)](i) increase and hyperplasia was similar to that observed in radioligand binding assays. In conclusion, these data provide evidence that the high-affinity [(3)H]-oxytocin binding site found in human USMC is a functional oxytocin receptor coupled to [Ca(2+)](i) increase and cell growth. Thus human USMC may prove to be a valuable tool in further investigation of the physiologic and pathophysiologic roles of oxytocin in the uterus. British Journal of Pharmacology (2000) 129, 131 - 139
AuthorsA Tahara, J Tsukada, Y Tomura, K i Wada, T Kusayama, N Ishii, T Yatsu, W Uchida, A Tanaka
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 129 Issue 1 Pg. 131-9 (Jan 2000) ISSN: 0007-1188 [Print] England
PMID10694212 (Publication Type: Journal Article)
Chemical References
  • Antidiuretic Hormone Receptor Antagonists
  • Ligands
  • Receptors, Oxytocin
  • Receptors, Vasopressin
  • Vasoconstrictor Agents
  • Arginine Vasopressin
  • Oxytocin
  • Calcium
Topics
  • Antidiuretic Hormone Receptor Antagonists
  • Arginine Vasopressin (pharmacology)
  • Binding, Competitive (drug effects)
  • Calcium (metabolism)
  • Cell Count
  • Cell Division (drug effects)
  • Female
  • Humans
  • Hyperplasia (chemically induced, pathology)
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Muscle, Smooth (cytology, drug effects)
  • Oxytocin (analogs & derivatives, pharmacology)
  • Receptors, Oxytocin (agonists, antagonists & inhibitors, drug effects)
  • Receptors, Vasopressin (agonists)
  • Second Messenger Systems (drug effects)
  • Uterus (cytology, drug effects)
  • Vasoconstrictor Agents (pharmacology)

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