Characteristics of endothelin-1 and endothelin-3 stimulation of phosphoinositide breakdown differ between regions of guinea-pig and rat brain.
Endothelin-3 was almost equipotent with endothelin-1 (ET-1) in stimulating phosphoinositide hydrolysis, as indicated by [3H]inositol phosphate formation, in cross-chopped slices of guinea-pig cerebellum, rat cerebellum and rat cerebral cortex. The magnitude of [3H]inositol phosphate formation was greatest in guinea-pig cerebellum, approximately 10-fold over basal levels. The similar level of [3H]IP1 accumulation produced by 1 mumol.l-1 ET-1 in rat cerebellum and cerebral cortex (circa 3-fold over basal) did not mirror the large difference in high-affinity [125I]ET-1 binding sites in the two regions. Moreover, the EC50 for ET-induced [3H]IP1 formation differed markedly between the three tissues (7 +/- 2 nmol.l-1 in rat cerebral cortex, 65 +/- 15 nmol.l-1 in guinea-pig cerebellum and greater than 200 nmol.l-1 in rat cerebellum). Only in rat cerebral cortex was the EC50 of the same order as has been reported for peripheral responses to ET-1.
Crawford
M L
ML
Department of Pharmacology, University of Cambridge, UK.
Hiley
C R
CR
Young
J M
JM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016232:Endothelins; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014757:Viper Venoms / Q000494:pharmacology
D016232:Endothelins; D007457:Iodine Radioisotopes; D010455:Peptides; D010716:Phosphatidylinositols; D014757:Viper Venoms; C057354:sarafotoxins s6