Endothelin Receptors and Signaling Mechanisms by David M. Pollock (auth.), David M. Pollock Ph.D., Robert F.

By David M. Pollock (auth.), David M. Pollock Ph.D., Robert F. Highsmith Ph.D. (eds.)

This ebook specializes in the big variety of intracellular occasions that take place because of endothelin receptor activation. This incorporates a dialogue of a few of the pathways in which endothelin prompts Ca2+ indications from numerous intra- and extracellular assets and the results of endothelin on ion channels and membrane functionality. furthermore, the mechanisms wherein endothelin impacts the ion delivery in the renal epithelium are coated, in addition to the sign transduction pathways activated via endothelin in either cardiac tissue and vascular soft muscle.

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As mentioned above, ET binding results in a stable receptor-ligand complex. However, how is this stable complex formed? Several hypotheses have been proposed. Studies using site-directed mutagenesis and ETA/ET Bchimeric receptors have suggested that ET ligands may interact with the receptors at more than one site,4'-42 which may contribute to the phenomenon. 43 Nambi et al4D have shown that there is a good correlation between the effect of guanine nucleotide on the binding of an agonist and the reversible/irreversible binding property of the agonist, hence implying that the interaction between ET receptors and the G proteins induced by the binding of an agonist may playa role in the formation of a stable complex.

It is generally thought that ET in circulation is a "spillover" from a local synthesis site, and the concentrations of ET at local sites are higher. Because of this, it is suggested that ET is not an endocrine factor, but mainly acts as a paracrine/autocrine factor. However, if receptor-bound ET is difficult to dissociate, and if the Kd values for ET binding are in the sub-picomolar range, then perhaps the systemic level of ET does have physiological and/or pathological significance even though it seldom rises above 50 pM.

5. Wada K, Tabuchi H, Ohba R et al. Purification of an endothelin receptor from human placenta. Biochem Biophys Res Commun 1990; 167:251-257. 6. Arai H, Hori S, Arimori I et al. Cloning and expression of a cDNA encoding an endothelin receptor. Nature 1990; 348:730-732. 7. Sakurai T, Yanagisawa M, Takuwa Y et al. Cloning of a eDNA encoding a nonisopeptide selective subtype of the endothelin receptor. Nature 1990; 1. 348:732-735. 8. Sudjarwo SA, Hori M, Tanaka T et al. Subtypes of endothelin ETA and ET B receptors mediating venous smooth muscle contraction.

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