Physiological Characteristics of Endogenous Sensitizer of β-Adrenergic Receptors (ESBAR) and Its Putative Components

Endogenous sensitizer of Beta-Adrenergic receptors (Esbar) and its analogs (Review)

“…The study of this issue mainly conducted experiments on LS NPRUH showing [61,68], that the blood serum of pregnant women and umbilical cord blood serum (as a source of ESBAR) and analogs of ESBAR -histidine and tyrosine, and in some cases tryptophan increase the inhibitory effect of above-threshold (but not maximum) concentrations of adrenaline, noradrenaline, and dopamine, but not enhance the inhibitory effects of synthetic beta 2 -agonists (ginipral and partusisten). This suggested that ESBAR and its analogs bind to the so-called amino acid site of beta 2 -AR and thus allosterically enhance its af inity to catecholamines, but not to synthetic agonists of adrenoceptor having different structure [61,68].…”

“…It has also been demonstrated [61,68], that the ability of ESBAR and its analogs (histidine, tryptophan, tyrosine) to improve the inhibitory effect of adrenaline is manifested not only on intact LS NPRUH having spontaneous CA, but also on LS NPRUH whose activity is enhanced arti icially, e.g., high potassium depolarization (KCl 60 mM) Krebs solution (рис. 3) or oxytocin (5x10-3 IU/mL).…”

“…3) or oxytocin (5x10-3 IU/mL). It speaks of the universality action of ESBAR and its analogs, capable in any environment to improve the ef iciency of beta 2 -AR activation In experiments with LS NPRUH was found [61,68], that the effect of ESBAR and its analogs observed relatively quickly -within the irst 1-3 minutes from the start of exposure. After a 20-minute application of ESBAR its effect lasts 10 min (after exposure to 500-and 103-fold dilutions of serum) or 80 min (after exposure to 100-fold dilutions serum).…”

“…ESBAR and its analogs exert their activity on the background of blockade of alpha-AR by nicergoline (10-6 g/mL) [68]. All this has allowed to argue [61,68], that ESBAR and its analogs are positive modulators of direct action, the effect of which is associated with increased af inity of receptor to agonist, to increase the ef iciency of the transmission signal from the beta 2 -AR inside the cell effectors and to counter the development of desensitization. Indeed, in experiments with LS NPRUH it is shown that histidine (3 х10-8, 3х10-7 and 3х10-6 g/mL, but not 3х10-11 g/ mL) inhibits the development of desensitization observed during the 30-minute continuous exposure at high concentration of adrenaline (10-6 g/mL) [68,75], and histidine (10-6 g /mL) counteracts desensitization, developed at 5-fold the short-term (10 min) effects of adrenaline (10-7 g/mL) as an inhibitor of spontaneous contractions [58].…”

“…During these years, efforts have been made to clarify the physiological role of ESBAR, in particular, the ability of ESBAR to improve the ef iciency of activation of beta 2 -AR of smooth muscle from pig coronary artery [20,21], the arteries and veins of human umbilical cord [22][23][24], cow renal artery [25][26][27][28], cow trachea [21,[29][30][31], rat stomach [32,33], and also myocardium of frog [34][35][36][37], rats [36][37][38][39][40][41][42] and humans [43][44][45] and human erythrocytes [46]. In addition, our efforts were made to ind analogs of ESBAR [21,27-29, 35-37,39-43,45-60], to study the mechanism of action of ESBAR and its analogs [36,[38][39][40][41][42][43][56][57][58][59][60][61], on the role of ESBAR in the pathogenesis of somatic diseases -coronary heart disease [62]…”