The significant role of endothelin-3 in potentiating electrically stimulated contractions in the rat iris sphincter.
1. We determined the endothelin (ET) receptor subtype involved in the facilitation of electrical field stimulation-(EFS) induced contraction using the ETB receptor agonist sarafotoxin S6c (STX S6c) and the ET receptor antagonists TTA-386 and bosentan. 2. ET-3-and ETB-receptor-selective agonist STX S6c enhanced EFS-induced contractions. The increasing effect of ET-3 was partially reduced by the desensitization to STX S6c or the ETA receptor antagonist TTA-386. After simultaneous treatment with TTA and desensitization, ET-3-induced potentiation was completely abolished. The combined ETA/B receptor blocker bosentan (Ro 47-0203) eliminated the ET-3-evoked neuronal effect. Both ETB and ETA receptors are involved in the facilitating effects of ETs on EFS contraction. 3. ET-3 immunoreactivity occurs densely in this tissue and was released from neuronal sites by electrical stimulation. We suggest that endogenous ET-3 has a more predominant role than ET-1.
Shinkai-Goromaru
M
M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Samejima
H
H
Takayanagi
I
I
D000818:Animals; D000077300:Bosentan; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000378:metabolism; D019334:Endothelin-3 / Q000378:metabolism / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D007498:Iris / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D019332:Endothelin-1; D019334:Endothelin-3; D016232:Endothelins; D011498:Protein Precursors; D017466:Receptors, Endothelin; D013449:Sulfonamides; D014757:Viper Venoms; C057354:sarafotoxins s6; D000077300:Bosentan