Endothelin receptors that modulate contraction of the rat fundus.
The present study aimed to characterize endothelin (ET) receptors mediating the effects of ET-1 in the rat fundic strip. Functional studies demonstrated that ET-1 and the ETB receptor-selective agonist sarafotoxin S6c elicit contraction of the rat fundic strip via high-affinity ETB receptors. Contraction was potentiated by the ETA receptor antagonist BQ 123 (10 microM) and the mixed antagonist bosentan (10 microM), suggesting that ET-1 also activates ETA and ETB receptors that inhibit contraction. This ET-1-mediated inhibition of contraction was blocked by an inhibitor of Ca(2+)-activated K+ channels, apamin (50 microM). Competitive binding studies revealed the presence of one BQ 123-sensitive and two BQ 123-insensitive binding sites that showed different affinity for ET-3 in the pM and nM range, respectively. These observations demonstrate the presence of multiple receptors in the rat fundus and suggest that smooth muscle contraction is counteracted by activation of Ca(2+)-activated K+ channels by ET-1.
Gray
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GA
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Breu
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V
Clozel
M
M
D000818:Animals; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology; D005748:Gastric Fundus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D017466:Receptors, Endothelin / Q000032:analysis / Q000502:physiology*
D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)