Are Several G Proteins Involved in the Different Effects of Endothelin‐1 in Mouse Striatal Astrocytes?

Abstract

High-affinity specific receptors of endothelin (ET-1) were identified on primary cultures of mouse embryo striatal astrocytes by binding experiments performed with 125I-ET-1. Stimulation of production of inositol phosphates, a biphasic increase of the intracellular calcium concentration, and inhibition of cyclic AMP accumulation were observed in the same cells under ET-1 stimulation. Pretreatment of these cells with Bordetella pertussis toxin affected these effects to different extends, an observation suggesting that they are mediated by multiple transduction pathways, possibly involving several guanine nucleotide-binding proteins.

Sensitivity of G‐protein involved in endothelin‐1‐induced Ca2+ influx to pertussis toxin in porcine endothelial cells in situ

“…InsP3 is believed to mediate the release of Ca2+ from intracellular storage site in endothelial cells (Newby & Henderson, 1990), presumably the endoplasmic reticulum. Simultaneously, ET-1 activates Ca2" influx probably via Ca2"-permeable channels (Goto et al, 1989;Kodama et al, 1989;Marin et al, 1991). However, in endothelial cells, no L-type voltage-dependent Ca2" chan-nels were detectable in electrophysiological studies (Newby & Henderson, 1990).…”

“…In various cell types ET-1 was found to mobilize Ca2+ from both intracellular and extracellular sources (Miasiro et al, 1988;Takuwa et al, 1990;Vigne et al, 1990;Thomas et al, 1991;Marin et al, 1991). ET-1 binds to the specific receptor to activate phospholipase C (PLC), which catalyzes hydrolysis of phosphatidyl inositol bisphosphate into inositol trisphosphate (InsP3) and diacylglycerol (Vigne et al, 1990; Thomas et al, 1991;Marin et al, 1991).…”

“…ET-1 binds to the specific receptor to activate phospholipase C (PLC), which catalyzes hydrolysis of phosphatidyl inositol bisphosphate into inositol trisphosphate (InsP3) and diacylglycerol (Vigne et al, 1990; Thomas et al, 1991;Marin et al, 1991). InsP3 is believed to mediate the release of Ca2+ from intracellular storage site in endothelial cells (Newby & Henderson, 1990), presumably the endoplasmic reticulum.…”

“…In smooth muscle cells, IAP had no effect on the response to ET-1 such as breakdown of phosphatidylinositol (PI) and the changes in [Ca2+J, (Mitsuhashi et al, 1989;Takuwa et al, 1990). In mouse striatal astrocytes (Marin et al, 1991) and in rat mesangial cells (Thomas et al, 1991), the responses to ET-1, such as elevation of [Ca2+ ] and PI turnover, are at least partially inhibited by IAP. In endothelial cells ETs inhibit adenylate cyclase via IAP-sensitive mechanisms (Ladoux & Frelin, 1991).…”

“…While involvement of a guanine nucleotide binding protein (G-protein) in the signal transduction pathway of ET-1 has been proposed, it is a matter of controversy whether or not this G-protein is pertussis toxin (IAP)-sensitive; results showing that it is IAP-sensitive (Kelly et al, 1990;Thomas et al, 1991;Marin et al, 1991), and that it is not IAP-sensitive Lysko et al, 1991) have been described. In the case of endothelial cells, the inhibitory effect of ET-1 on adenylate cyclase was found to be IAP-sensitive, thereby indicating the involvement of IAP-sensitive G-protein (Ladoux & Frelin, 1991).…”