Expression and function of endothelins, endothelin receptors, and endothelin converting enzyme in the porcine trachea.
Endothelins (ETs) can modulate the airway smooth muscle tone. Using simultaneous measurements of cytosolic Ca2+ concentration ([Ca2+]i) and tension as well as the reverse transcription polymerase chain reaction (RT-PCR), we examined ET systems in the porcine trachea. In the functional study, the application of ET-1, ET-3 or sarafotoxin S6c (S6c) caused increases in [Ca2+]i and tension, in a concentration-dependent manner. These ET ligands were found to increase the Ca2+ sensitivity of the myofilament of the tracheal smooth muscle cells (SMCs). The contractions induced by ET-1 (10(-7) M), an ET receptor (ET-R) non-selective agonist, were much greater than those induced by S6c, an ET(B)-R selective agonist. BQ-123 (10(-6) M), an ET(A)-R antagonist, inhibited the ET-1 induced contraction. These functional experiments suggested the presence of both functioning ET(A)- and ET(B)-Rs in tracheal SMCs. RT-PCR experiments revealed that the tracheal SMCs expressed both ET(A)-R and ET(B)-R mRNAs, while tracheal epithelial cells (EpCs) predominantly expressed ET(A)-R mRNA. The porcine tracheal SMCs and EpCs also expressed pre-pro ET-1 (ppET-1), ppET-3, and endothelin converting enzyme-1 (ECE-1) mRNAs. These results suggested that ETs induce contraction of porcine tracheal SMCs not only by increasing [Ca2+]i but also increasing the Ca2+ sensitivity of the myofilament and that ETs could potentially be the autocrine and/or paracrine transmitters to regulate the contraction in the porcine airway smooth muscle.
Yoshimura
H
H
Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nishimura
J
J
Sakihara
C
C
Kobayashi
S
S
Takahashi
S
S
Kanaide
H
H
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D019898:Autocrine Communication; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism*; D008666:Metalloendopeptidases; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology*; D019899:Paracrine Communication; D017466:Receptors, Endothelin / Q000378:metabolism*; D013552:Swine; D014132:Trachea / Q000502:physiology*
D016232:Endothelins; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes