Mechanism of rat uterine smooth muscle contraction induced by endothelin-1.
1. Endothelin (ET)-1 has been demonstrated to cause contraction of uterine smooth muscle. We investigated the role of ET receptor subtypes (ETA and ETB receptors) in ET-1-induced contraction of rat uterine smooth muscle by using the ETA receptor antagonist BQ-123 and the ETB receptor agonist BQ-3020. 2. ET-1 caused a contraction with superimposed oscillations of the rat isolated uterus suspended in Krebs-Ringer solution; both the amplitude of contraction as well as the oscillation frequency increased in a dose-dependent manner (10(-11)-10(-7)M). 3. BQ-123 (10(-6)M) markedly shifted the dose-response curve of ET-1 for both contractile effects and oscillation frequency to the right. 4. BQ-3020 (10(-11)-3 x 10(-7) M) did not cause uterine contraction; neither did it affect the dose-response curve of ET-1 for either the contractile effect or the increase in oscillation frequency. Thus, stimulation of ETB receptors is not involved in these responses. 5. The present findings suggest that ET-1-induced contractile responses and the increase in oscillation frequency in rat uterine smooth muscle is mediated through ETA receptors, and that ETB receptors play no role in these responses.
Tsunoda
H
H
Department of Obstetrics and Gynecology, University of Tsukuba, Ibaraki, Japan.
Miyauchi
T
T
Fujita
K
K
Kubo
T
T
Goto
K
K
D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000502:physiology; D014590:Uterine Contraction / Q000187:drug effects*
D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)