Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa" (CSIC–UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, and Departamento de Bioquímica y Biología Molecular I, Facultad de Químicas, Universidad Complutense de Madrid, Madrid, Spain.

Correspondence: R Edgardo Catalán, Departamento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa" (CSIC–UAM), E-28049 Madrid, Spain.

Received 23 May 1995; Revised 21 February 1996; Accepted 22 February 1996.

Abstract

Treatment of brain microvessels with the three endothelin (ET) isoforms resulted in an increase of phosphoinositide turnover by activation of phospholipase C in a dose- and time-dependent manner. Both ET-1 and ET-2 are maximally effective, whereas the effect evoked by ET-3 was smaller. Concomitantly, there was an enhanced production of a platelet-activating factor (PAF)-like material. This was identified by standard and biological probes in platelets, such as induction of aggregation, phosphatidic acid (PA) production, increase of endogenous protein phosphorylation, and reversal of these responses by a PAF antagonist. The effects evoked by endothelins on phosphoinositide metabolism and PAF production were, to a certain extent, dependent on the presence of extracellular Ca²⁺. In addition, ET induced changes in Ca²⁺ dynamics, evoking an initial and rapid intracellular mobilization and influx of Ca²⁺ and, later, a maintained Ca²⁺ influx. These findings contribute to the understanding of the pathophysiological role of ET in the blood-brain barrier (BBB).