Endothelin-1 and -2: two amino acids matter.
Life Sci
; 91(13-14): 607-12, 2012 Oct 15.
Article
in En
| MEDLINE
| ID: mdl-22406300
ABSTRACT
AIMS:
Endothelin-1 (ET-1) and endothelin-2 (ET-2; Trp(6)Leu(7)ET-1) are expressed by different cell types, but are considered to display identical pharmacological properties on endothelin receptors. We studied agonist-dependent aspects of endothelin(A) (ET(A))-receptor function and the importance of amino acids 6 and 7 of ET-1 and ET-2 in this respect. MAINMETHODS:
We used isolated rat mesenteric resistance arteries in wire myographs, in a setting that minimizes influences of endothelium and sensorimotor nerves, to study arterial smooth muscle ET(A)-receptor-mediated vasomotor responses, to ET-1, ET-2 and chimeras thereof (Trp(6)ET-1 and Leu(7)ET-1). KEYFINDINGS:
ET-1 and ET-2 cause arterial contractions with comparable sensitivities and maximal responses. BQ123 (ET(A)-antagonist) reduces sensitivity to ET-1 more potently than that to ET-2 (pK(B) 7.1 ± 0.2 versus 5.6 ± 0.4). However, 1 µM BQ123 relaxes maximal contractile responses to ET-2 more markedly than those to ET-1. Leu(7)ET-1 is a contractile agonist with lower potency and similar maximal effect compared to ET-1 and greater sensitivity to BQ123 than ET-2. Up to 256 nM Trp(6)ET-1 did not cause contraction and did not antagonize arterial responses to ET-1.SIGNIFICANCE:
Arterial smooth muscle ET(A)-receptor function displays agonist-dependent aspects. This involves roles of amino acids on position 6 and 7 of the endothelin sequence. Agonist-dependent pathologies may benefit from the design of specific, agonist-selective ET-receptor antagonists.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endothelin-1
/
Endothelin-2
/
Receptor, Endothelin A
/
Mesenteric Arteries
Limits:
Animals
Language:
En
Journal:
Life Sci
Year:
2012
Document type:
Article
Affiliation country:
Netherlands