8-Guanidinoethyl sulfonate

I will also describe a simple method of modifying taurine content, using a compound, guanidinoethyl sulfonate, which is a competitive antagonist of taurine transport, and which is also, in part, a physiological antagonist. 

It is apparent that the heart has the capability to biosynthesize taurine, and also to take it up from the circulation. We have initiated quantitative studies as to the relative contributions of these two sources. Rats were maintained on a diet containing taurine of a known specific activity. Rats were sacrificed at intervals, and the specific activity of taurine determined in various tissues. From this, the content of taurine that had been derived from dietary sources could be calculated, as shown in Table 1. By the 15th day, in all tissues except the liver, influx had accounted for 1/3 of the total taurine. The remainder must either arise from biosynthesis, or be part of the taurine pool present in the tissue at the beginning of the experiment. These data, at face value, appear to be inconsistent with the results of experiments described below using guanidinoethyl sulfonate, a transport inhibitor of taurine. 

Hypotaurine 3-Alanine 3-Guanidinoethyl sulfonate 3-Guanidino-propionate... 

Active transport of 3-alanine occurs in the heart apparently by the same system that transports taurine. However, as shown in figure 4, there is a nonsaturable component to transport. The pKa of 3-alanine is 3.6. Thus, at a pH of 7.2, the proportion of 3-alanine with a non-ionized acid function is 125 times higher than for an equivalent concentration of taurine. Guanidinoethyl sulfonate is transported in place of taurine by a saturable process (fig. 5). The Lineweaver-Burk plot for transport is shown in figure 5. Over the concentration range 0-400yM, transport occurs by a one component system with an affinity (Km) of 153 yM, and a Vmax of 65 nmole/g dry weight/min. 

Alanine has potential usefulness as a transport inhibitor. However, it has physiological and pharmacological actions of its own, and there is a nonsaturable component to its uptake by the heart. Guanidinoethyl sulfonate, on the other hand, does not occur... 

Fig. 5. Lineweaver-Burk plot of guanidinoethyl sulfonate transport in the isolated, perfused heart.

Despite these dramatic modifications in taurine content, the only gross behavioral abnormality noted was hyperactivity. However, no specific behavioral tests were applied. Intracerebral injections of 9.2 ymole taurine into seizure susceptible rats cause marked attenuation of seizure severity, in keeping with the anticonvulsant actions of taurine shown in a number of laboratories (Laird and Huxtable 1976). Similar injections of guanidinoethyl sulfonate lead to intense seizure activity within five seconds, before the injection had been completed. The animal suffered continuous... 

Table 4. Effect of Guanidinoethyl Sulfonate and Taurine Free Diet on Tissue Taurine Content...

Alanine, hypotaurine, guanidinoethyl sulfonate and guanidino-propionate are inhibitors of taurine in the Langendorff perfused rat heart. 

Guanidinoethyl sulfonate is transported into the rat heart by a one component saturable system. The transport of 6-alanine into the heart has both a saturable and a non-saturable component. ... 

Marked depletion of tissue taurine concentrations occur within days when rats and other small mammals are maintained on drinking water containing 1% guanidinoethyl sulfonate. 

Guanidinoethyl sulfonate administration is proposed as a simple and effective method for the experimental manipulation of taurine concentration. 

J. Azari, J. Bahl, and R. Huxtable, Guanidinoethyl sulfonate and other inhibitors of the taurine transporting system in the heart, Proc. Western Pham., Soc. 22 in press (1979). 

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