Cardiac Glycoside Receptor

E. Erdman, K. Werdan, L. Brown (1985). Multiplicity of cardiac glycoside receptors in the heart. Trends Pharmacol. Sci. 6 293-295. 

Fullerton DS, Griffin JF, Rohrer DC, et al. Using computer graphics to study cardiac glycoside-receptor interactions. Trends Pharmacol Sci 1985 6 279-282. 

Haustein, K.-O. (1984) in Cardiac Glycoside Receptors and Positive Inotropy (Erdmann, E., ed.), pp. 147-153, SteinkopffVerlag, Darmstadt. 

The pharmacological receptor of cardiac glycosides is the sarcolemmal Na+/K+-ATPase expressed on most eucaryotic membranes. It was characterised biochemically in 1957 by J. Skou, who was awarded with the Nobel Prize in chemistry in 1997. The sodium... 

Parasympathomimetics and sym-pathomimetics act at membrane receptors for visceromotor neurotransmitters. The plasmalemma also harbors the sites of action of cardiac glycosides (the Na/K-ATPases, p. 130), of Ca + antagonists (Ca2+ channels, p. 122), and of agents that block Na channels (local anesthetics p. 134, p. 204). An intracellular site is the target for phosphodiesterase inhibitors (e.g., amrinone, p. 132). 

Taurine (2-aminoethanesulfonic acid 4.235) is an inhibitory neurochemical that probably acts primarily as a neuromodulator rather than a neurotransmitter. It is formed from cysteine, and its accumulation can be prevented by the cardiac glycoside ouabain. Although receptor sites and specific actions cannot be elucidated without an antagonist, taurine has been implicated in epilepsy and, potentially, in heart disease. There are a large number of physiological effects attributed to taurine, among them cardiovascular (antiarrythmic), central (anticonvulsant, excitability modulation), muscle (membrane stabilizer), and reproductive (sperm motility factor) activity. Analogs of taurine, phthalimino-taurinamide (4.236) and its iV-alkyl derivatives, are less polar than taurine and are potent anticonvulsant molecules. 

The influence of a series of 12 cationic amphiphilic drugs, including anesthetics, an-tiarrhythmics, and psychotropic agents, has been studied on the binding equilibrium of [3H]-ouabain to membrane suspensions of guinea-pig myocardium. The binding of 3H-labeled ouabain to cardiac Na+,K+-ATPase is a method used to characterize the interaction between cardiac glycosides and their receptor. 

Toxins in general are potent poisons. Nevertheless, the selectivity of action of some of these toxins means they have been harnessed in medical therapeutics (and even more widely in experimental pharmacology and physiology). Toxins that have been, or still are. us in medicine include atropine, botulinum toxin, cardiac glycosides, coichidne, eserine, hyoscine, picrotoxin, morphine, ouabain, strychnine, veratridine, vinca alkaloids and many more. All these work by an action at a defined molecular site, whether ion channel, neurotransmitter receptor, enzyme, pump or intracellular organelle. Those toxins that work at nonneuronal, or not specifically at neuronal sites (e.g. cholera toxin, pertussis toxin, cardiac glycosides, phospholipases) are discussed under TOXINS. 

All cardiac glycosides have qualitatively the same effect. Primarily the systolic contraction of the heart muscle is strengthened. The mode of action of the cardiac glycosides, which is not known in all details, depends on rhythmic intracellular liberation of calcium-ions by inhibition of the calciumion outflow and an increase in the inflow of calcium-ions into the cell. This takes place by inhibition of Na+/K-r-activating membrane-ATP-ase. (Digitalis receptor). The concentration of Na+ is increased and that of K-r is decreased intracellularly. In this way the myosin-ATP-ase is activated with improved use of ATP, which gives increased power of contraction by facilitated reaction between actin and myosin. 

Drug groups used to control cardiac failure are cardiac glycosides, diuretics, ACE inhibitors and angiotensin II receptor antagonists. 

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