Lysine vasopressin-induced increases in porcine myometrial contractility and intracellular Ca2+ concentrations of myometrial cells: involvement of oxytocin receptors.
The present study was undertaken to investigate whether lysine vasopressin (LVP) induces porcine myometrial contractions by activating vasopressin or oxytocin (OT) receptors. Both LVP (3 x 10(-9)-10(-6) M) and OT (3 x 10(-11)-10(-8) M) increased contractility dose-dependently in myometrium from both the luteal phase and prepartum period. Comparison of EC50s showed that OT was 75 and 57 times more potent than LVP in increasing myometrial contractility in pregnant and nonpregnant sows, respectively. L-366,948 (10(-8), 3 x 10(-8), 10(-7) M), a highly selective OT receptor antagonist, inhibited LVP- and OT-induced increases in myometrial contractility dose-dependently in both pregnant and nonpregnant tissues with similar antagonist affinity values (pA2). The V1 antagonist d(CH2)5[D-[Tyr(Me)2]AVP also antagonized both LVP- and OT-induced increases in myometrial contractility, but higher concentrations (10(-7) and 10(-6) M) were required to achieve the antagonism. The V2 antagonist Aaa-D-Tyr(Et)-Phe-Val-Asn-Abu-Pro-Arg-Arg-NH2 (10(-6) M) did not alter this effect of LVP and OT. LVP (10(-9)-10(-6) M) and OT (10(-10)-10(-7) M) also increased intracellular Ca2+ ([Ca2+]i) concentrations in porcine myometrial cells from sows during the prepartum period in a dose-dependent manner, with OT being 14 times more potent than LVP. L-366,948 (10(-9)-3 x 10(-8) M) antagonized the effect of OT (10(-7) M) and LVP (10(-6) M) in a similar dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011, USA.
Zhuge
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Hsu
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D000595:Amino Acid Sequence; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D002118:Calcium / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008236:Lypressin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009215:Myometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010121:Oxytocin / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000494:pharmacology; D011869:Radioligand Assay; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013552:Swine; D014590:Uterine Contraction / Q000187:drug effects*
D065092:Antidiuretic Hormone Receptor Antagonists; D010456:Peptides, Cyclic; D018045:Receptors, Oxytocin; C066873:L 366948; D010121:Oxytocin; D008236:Lypressin; D002118:Calcium