Ouabain receptor

No study on the digoxin-like activity of hattalin has been reported though it has affinity for the ouabain receptor. 

Tamplin et. al. (54) observed that V. cholerae and A. hydrophila cell extracts contained substances with TTX-like biological activity in tissue culture assay, counteracting the lethal effect of veratridine on ouabain-treated mouse neuroblastoma cells. Concentrations of TTX-like activity ranged from 5 to 100 ng/L of culture when compared to standard TTX. The same bacterial extracts also displaced radiolabelled STX from rat brain membrane sodium channel receptors and inhibited the compound action potential of frog sciatic nerve. However, the same extracts did not show TTX-like blocking events of sodium current when applied to rat sarcolemmal sodium channels in planar lipid bilayers. 

To characterize the preparation, determine marker enzymes, e.g., p-nitrophenyl phosphatase (PNPase), ouabain-sensitive Na,K-dependent ATPase, or dihydropyridine receptor complex (L-type voltage dependent calcium channel). 

Nurnberger J Jr, Jimerson DC, Allen JR, et al Red cell ouabain-sensitive Na -K -adenosine triphosphatase a state marker in affective disorder inversely related to plasma cortisol. Biol Psychiatry 17 981-992, 1982 Nutt D, Montgomery SA Moclobemide in the treatment of social phobia. Int Clin Psychopharmacol 11 (suppl 3 77-82, 1996 Nutt DJ, Glue P, Lawson GW, et al Elumazenil provocation of panic attacks evidence for altered benzodiazepine receptor sensitivity ion panic disorder. Arch Gen Psychiatry 47 917-925, 1990... 

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. 

Orgado et al, 2003), (ii) exogenous anandamide reduced ouabain-induced neuronal damage in 1- and 7-day-old rat pups through activation of CB1 receptors (van der Stelt et al., 2001), and (iii) a dramatic increase of anandamide precursors has been observed in the infant rat brain after head trauma (Hansen et al., 2001). 

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. 

Since for heart glycosides the same reaction via receptors in the membrane is also supposed, similar studies have been carried out by T. W, Smith and his coworkers (94) with digoxin and ouabain bound to a polymer (to albumine or polylysine via different spacers). From the nearly complete disappearance of the activity it had to be concluded these receptors, if localized in the cell membrane, are not present in their surface. 

Simple mathematical calculations by the first pharmacologists in the 1930s indicated that structurally specific drugs exert their action in very small doses and do not act on all molecules of the body but only on certain ones, those that constitute the drug receptors. For example, Clark [407] calculated that ouabain applied to the cells of the heart ventricle, isolated from the toad, would cover only 2.5% of the cellular surface. These observations prompted Clark [407,408] to apply the mathematical approaches used in enzyme kinetics to the effects of chemicals on tissues, and this formed the basis of the occupancy theory for drug-receptor interaction. Thus, pharmacological receptor models preceded accurate knowledge of receptors by many years. 

Van Huysse JW, Leenen FH (1998) Role of endogenous brain ouabain in the sympathoexcitatory and pressor effects of sodium. Chn Exp Hypertens 20 657-667 Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urban P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison IS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310 329-332... 

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. 

Mest, H.J., Thomsen, P., Raap, A., 1995. Antiarrhythmic effect of the selective I j-imidazoline receptor modulator moxonidine on ouabain-induced cardiac arrhythmia in guinea pigs. Ann. N. Y. Acad. Sci. 763, 620-633. 

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