H. A. S. VAN DEN BRENK 



are of much greater specificity and importance. These receptors are present 

 on smooth muscle cells, and contraction of the actomyosin filaments in the 

 cell is apparently induced by Ca++ and Mg++ ions in the presence of ATP, 

 and not by the amine itself^^, the latter being considered to combine with the 

 receptor and lead to an increase in meml^rane permeability with passage of 

 water and metallic ions into the cell-^. 



D receptors — If these receptors are blocked by a specific antimetabolite 

 such as lysergic acid diethylamide (LSD), its brominated derivative (BOL) 

 or a highly specific serotonin derivative, l-benzyl-5-methoxy-2N, N-trimethyl 

 tryptamine (BAS), prior to administration of 5-OHT in rats, the radio- 

 protective effect of the indole can be almost completely annulled ^^. The 

 relative molecular amounts of 5-OHT and the antimetabolite administered 

 decide the degree of protection, but is difficult to determine with any accuracy 

 in vivo. However, the approximate molar ratios which give maximal antago- 

 nism, for the three antimetabolites studied are given in Table 1. 



Table 1 



The approximate 'inhibitory indices' given are subject to considerable error, 

 owing to the nature of the experimental conditions, but seem to follow the 

 more accurate pharmacological pattern, obtained in vitro. The antimetabolites 

 administered alone, before or after irradiation, do not significantly influence 

 radiation lethality, but tend to diminish diarrhoea — particularly LSD and 

 BOL. 



The result with BAS is particularly interesting in that this compound, is a 

 substituted serotonin which Woolley has stated to be very specific in blocking 

 5-OHT, and even inactive against tryptamine itself^^. 



The j8-haloalkylamines, are adrenergic blocking agents, and our work 

 has been confined to the use of dibenzyline, which in doses of 0-25 mg failed 

 to reverse the protective effect of 5-OHT, but further experimental work is 

 in progress with larger doses, given at various times before the challenge dose 

 of 5-OHT. 



M receptors — Atropine failed to modify 5-OHT protection in rats in doses 

 of 0-25 mg, 10 minutes preceding irradiation. It would appear that these 

 receptors are relatively unimportant in the radio-protective action under 

 consideration. 



Specificity of Antimetabolites of 5-OHT and Histamine 



To compare the inhibition of these two radio-protective amines, the inhibitory 

 effects of an antisei'otonin and an antihistamine, were tested against histamine 

 and 5-OHT respectively. It has been found that whilst Promezathine reverses 



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