BK2 but not BK1 receptors mediating contractile response in human umbilical arteries: role of thromboxane A2.
Bradykinin receptors have been divided into B1 and B2 subtypes. The aim of this study on human umbilical arteries was: i) to compare the recognition properties of the mediating contractions of bradykinin receptors; and ii) to assess the possible role of thromboxane A2 in a bradykinin-induced contraction of smooth muscle. Umbilical arteries were dissected and mounted in organ baths for isometric measurement of force. Our results showed that the B1 agonist [Sar1dPhe8desArg9]-bradykinin had no effect on the concentration-response 10(-9)-3 x 10(-5) mM. Cumulative additions of bradykinin (10(-9)-3 x 10(-5) mM) and of the B2 agonist [Hyp3TyrMe8]-bradykinin (10(-9)-3 x 10(-5) mM) produced dose-dependent contractions. Dose response curves to bradykinin (10(-9)-3 x 10(-5) mM) were not significantly altered by the presence of B1 selective antagonist [des-Arg9, Leu8]-bradykinin (10(-5) mM), or by the selective B2 antagonist [Thi(5,8), D-Phe7]-bradykinin (10(-5) mM). However, Hoe 140 D-Arg-[Hyp3, Thi5,D-Tic7, Oic8]-bradykinin, an antagonist of B2 responses, significantly inhibited bradykinin-induced contraction. The responses to bradykinin were unaffected by indomethacin (10(-4) mM), dazoxiben (10(-5) mM) or even by nordihydroguaiaretic acid (10(-5) mM). However, bradykinin contractions were antagonized in a noncompetitive manner by quinacrine (10(-5) mM). These results showed that bradykinin contracts human umbilical arteries essentially through B2 receptors. Moreover, the responses to bradykinin are unlikely to be mediated by the cyclooxygenase/lipooxygenase pathway. The inhibitory effects of quinacrine may be due to a specific or nonspecific effect at a cellular level on smooth muscle contractility, or due to a direct action to block Ca2+ influx at membrane level.
Laboratoire de Physiologie & Pharmacologie Cardiovasculaire, Montceaules-Mines, France. alberto.tiritilli@ch-montceau71.fr
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Tiritilli
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El Habach
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Duret
D001920:Bradykinin / Q000819:agonists / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000166:cytology / Q000293:injuries; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011796:Quinacrine / Q000494:pharmacology; D043783:Receptor, Bradykinin B1 / Q000502:physiology; D043782:Receptor, Bradykinin B2 / Q000187:drug effects / Q000502:physiology*; D013928:Thromboxane A2 / Q000502:physiology; D014469:Umbilical Arteries / Q000187:drug effects*
D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D007093:Imidazoles; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C495449:bradykinin, Hyp(3)-TyrMe(8)-; C029166:dazoxiben; C072121:bradykinin, Sar-(D-Phe(8))des-Arg(9); D013928:Thromboxane A2; D009637:Masoprocol; C065679:icatibant; C053426:bradykinin, (Thi-Ala)(5,8)-Phe(7)-; D011796:Quinacrine; D001920:Bradykinin; D007213:Indomethacin