Human endothelin ETA receptor antisense oligodeoxynucleotides inhibit endothelin-1 evoked vasoconstriction.
Antisense oligodeoxynucleotides to endothelin ETA receptor mRNA were used to characterize vascular smooth muscle receptors. The concentration-response curve showed a significant attenuation of endothelin-1-induced contraction in circular segments of the human superficial temporal artery. Endothelin ETB receptor antisense or mismatch oligodeoxynucleotides showed no alteration of the endothelin-1-induced contraction. Complementary experiments with the selective endothelin ETA receptor antagonist FR139317 demonstrated a shift of the concentration-response curve to the right in a competitive manner (pA2 = 6.93). The specific method of using the receptor antisense oligodeoxynucleotides approach revealed the presence of endothelin ETA receptors mediating contraction in the human superficial temporal artery.
Adner
M
M
Department of Internal Medicine, University Hospital of Lund, Sweden.
Erlinge
D
D
Salford
L G
LG
Yee
F
F
Wahlestedt
C
C
Edvinsson
L
L
D001381:Azepines / Q000494:pharmacology; D001483:Base Sequence; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D007211:Indoles; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D017466:Receptors, Endothelin; C079574:FR 139317