PT  - JOURNAL ARTICLE
AU  - Allcock, G H
AU  - Battistini, B
AU  - Fournier, A
AU  - Warner, T D
AU  - Vane, J R
TI  - Characterization of endothelin receptors mediating mechanical responses to the endothelins in the isolated stomach strip of the rat.
DP  - 1995 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 120--126
VI  - 275
IP  - 1
4099  - http://jpet.aspetjournals.org/content/275/1/120.short
4100  - http://jpet.aspetjournals.org/content/275/1/120.full
SO  - J Pharmacol Exp Ther1995 Oct 01; 275
AB  - We have characterized the receptors mediating the mechanical responses of the isolated stomach strip to endothelin-1 (ET-1), endothelin-3 (ET-3) and the ETB-selective receptor agonists sarafotoxin 6c (SX6c) and IRL 1620. As antagonists we used BQ-123 (ETA receptor selective), BQ-788 (ETB receptor selective) and PD 145065 (ETA/ETB receptor nonselective). We have also compared the responses of the mature peptides to their precursors human big ET-1(1-38), porcine big ET-1(1-39) and big ET-3(1-41) amide. ET-1, ET-3, SX6c and IRL 1620 produced equipotent concentration-dependent contractions of the rat stomach strips that were antagonized by PD 145065 (10(-5) M) or BQ-788 (10(-5) M) but not by BQ-123 (10-5 M). This indicates that the ETB receptor mediates contractions to the endothelins in this preparation. In preparations precontracted with PGE2 (3 x 10(-8) M), ET-1, but not SX6c (both 3 x 10(-9) M), caused a transient (< 2 min) relaxation (approx. 40% of the induced tone). This relaxation was antagonized by BQ-123 (10(-5) M) but prolonged by BQ-788, and therefore mediated by ETA receptors. A single administration of 3 x 10(-7) M ET-1, ET-3, SX6c or IRL 1620 produced contractions that reached a maximal response after 1 to 3 min. The contractions were not maintained, although responses to ET-1 or ET-3 lost their tone less rapidly than those to SX6c or IRL 1620.(ABSTRACT TRUNCATED AT 250 WORDS)