y. i

FIGURE 15-11 Schematic diagram of the ANP hormonal system. An elevated vascular volume results in cleavage and release of atriopeptin, which acts on the kidney (glomeruli and papilla) to increase the glomerular filtration rate (GFR) so as to increase renal blood flow (RBF), increase urine volume (UV) and Na+ excretion (UNa), and decrease plasma renin activity. Natriuresis and diuresis are also enhanced by the suppression of aldosterone production and its actions and by the release from the posterior pituitary of arginine vasopressin (AVP). Diminution of vascular volume provides a negative feedback signal that suppresses circulating levels of atriopeptin. Modified from Needleman, P., and Greenwald, J. E. (1986). Atriopeptin: A cardiac hormone intimately involved in fluid, electrolyte, and blood pressure homeostasis. New Engl. J. Med. 314, 828-834.

form of ET-1. Processing of this "intermediate" ET-1 by a pair of dibasic specific endopeptidases (at Lys51-Arg52 and Arg91-Arg92) generates the 38-amino-acid polypeptide pro-ET-1, which is sometimes referred to as "big" ET-1. Pro-ET-1 represents the secreted form of endothelin; further processing occurs outside the endothelin cell by the action of a putative endothelin-converting enzyme (ECE). The sites of ECE cleavage for the proendothelins are shown in Figure 15-12. Pro-ET-1 has only 1% of the biological activity of mature ET-1.

3. Biological Actions of Endothelins

In endothelial cells ET-1 is predominant, while ET-2 and ET-3 are virtually undetectable. The mRNAs for all three endothelins are present in human kidney and jejunum, while in the nervous system the mRNA for ET-1 is the major species. The variable but diverse distribution of the ET isoforms suggests that ET has multiple functions both inside and outside the vascular system.

Radioligand-binding studies with the isoforms of ET have indicated the presence of two classes of receptors. Type I receptors are involved with vasoconstriction, bronchoconstriction, and stimulation of aldosterone biosynthesis. Type II receptors are linked to the inhibition of platelet aggregation and vasorelaxation. Through molecular cloning of ET receptors, the deduced amino acid sequence of seven ET receptors has been elucidated; they can be divided into two classes designated ETA and ETB (see Table 15-8). Both classes of endothelin receptors belong to the seven-transmembrane, G-protein-coupled superfamily (see Figure 1-23).

The current view is that ETA endothelin receptors mediate the paracrine (vasoconstrictor) actions of ET-1, while the ETB receptors mediate the more "nonselective" actions of endothelins, including autocrine actions related to endothelin-relaxing factor (EDRF) and vasodilation (see Figure 15-13).

Occupancy of the endothelin receptors is coupled to the activation of phospholipase C via a pertussis

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Cure Tennis Elbow Without Surgery

Cure Tennis Elbow Without Surgery

Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.

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