HOWARD M. LENHOFF 209 



of the subsequent events leading to mouth opening. The values for 

 ti (0.4 to 1.0 minutes) may represent, for the most part, the latter 

 events. 



Large values of ti (those greater than 2.0 minutes) indicate that 

 the experimental conditions for the feeding reflex are not optimal. 

 For example, it takes longer for the mouth to open at low gluta- 

 thione concentrations (Table 1, expt. e) or in the presence of a 

 competitive inhibitor (Table 1, expt. f) than at excess glutathione 

 concentrations under optimum conditions. Similarly, cellular poi- 

 sons, such as N-ethyl maleimide or heavy metals, also cause an 

 increase in ti (9). Further, Hydra in distilled water take longer to 

 respond than do Hydra in distilled water containing added calcium 

 (10). In the cases mentioned here, it would appear that the large 

 values of t. result from the interference with the activation of a 

 sufficient number of functional receptor sites needed to elicit an 

 optimally rapid response. Another cause of a delay in mouth opening 

 might stem from interference with some of the cellular events 

 initiated by the combination of glutathione with its receptor. 



At sub-optimal concentrations of glutathione (Table 1, expt. e, 

 and Fig. 3 at concentrations less than 5 ■ 10"*' M glutathione) the 

 tf-ti values were small in comparison to those obtained at higher 

 glutathione concentrations. These results show that graded responses 

 can occur when conditions are not optimum. In addition, it is gen- 

 erally observed that the larger the value of ti, the smaller the value 



of tf-ti. 



EFFECT OF GLUTAMIC ACID AND 

 GLUTATHIONE ANALOGS 



Using glutathione analogs, we have undertaken a study of the 

 size and configuration of the glutathione molecule necessary for 

 activation of the response. The results, summarized in Table 2, 

 show that the glutathione-receptor has a most unusual specificity 

 compared to proteins which react with glutathione ( 13 ) . The recep- 

 tor (a) is not dependent upon the sulfhydryl moiety of glutathione 

 for activation, (b) has a high order of specificity for the structure 

 of the tripeptide "backbone" of glutathione, and (c) is inhibited 

 by glutamic acid. 



