Characteristics of endothelin-1 and endothelin-3 stimulation of phosphoinositide breakdown differ between regions of guinea-pig and rat brain

Abstract

Endothelin-3 was almost equipotent with endothelin-1 (ET-1) in stimulating phosphoinositide hydrolysis, as indicated by [3H]inositol phosphate formation, in crosschopped 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 μmol -I ⁻¹ ET-1 in rat cerebellum and cerebral cortex (circa 3-fold over basal) did not mirror the large difference in high-affinity [1 a sI]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 · 1⁻¹ in rat cerebral cortex, 65± 15 nmol · 1⁻¹ in guinea-pig cerebellum and > 200 nmol·I ⁻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.