Endothelins stimulate phosphoinositide breakdown in the rat spinal cord through ETA receptors.
In rat spinal cord slices, endothelin-1 (ET-1) and -3 (ET-3), sarafotoxin 6c (STX-6c), and the ETB receptor agonist IRL-1620 produced increases of [3H]inositol phosphate (IP) accumulation with the following rank order of potency: ET-1 > ET-3 >> STX-6c = IRL-1620. The ET-1- and ET-3-induced IP accumulations were blocked by BQ-123, a selective ETA antagonist, with a similar inhibition constant (IC50 16.7 +/- 3.4 microM and 8.0 +/- 1.6 microM, respectively) whereas BQ-788, a selective ETB antagonist, was inactive. These data indicate that ET-induced IP accumulation in rat spinal cord is mediated by an ETA receptor. The present study is in agreement with ETA receptor-mediated cardiovascular changes induced by intrathecal injection of ET-1 in the conscious rat.
Poulat
P
P
Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada.
D'Orléans-Juste
P
P
de Champlain
J
J
Couture
R
R
D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D016232:Endothelins; D010716:Phosphatidylinositols; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin