RAlMC)-PR()li:C;ri\K AUIION Ol- 5-HVDR()X\ l RMTAMIM': 



if administered five to ten minutes l)ef()re irradiation {vide supra) and Com- 

 pound 4H 80 (200 /ig) administered seven minutes l)efore irradiation, gave 

 more substantial protection (20 to 30 per cent survivors at 30 days, 1000 r 

 whole-bocK inadiation) — largely attributable to the large amounts of 

 histamine liberated. Animals acutely depleted of histamine by Compound 

 48 80 show a slight l)ut not significant increase in lethality i'-*. Animals pre- 

 treatcd w ith ii^onia/id and given reserpinc 30 minutes preceding irradiation, 

 show a slight but significant protection, with a doubling of the mean survival 

 for 1000 r whole-body dose. 



To summarize the results obtained for endogenous 5-OHT in radiation 

 protection, it would appear that the concentration of 'bound' 5-OHT in 



t t t t t t t t t t tj, t. 



5-OHT after reserpine 

 31 26 22 18 15 11 8 



10 " 10 ' 10 

 5-OHT 



5 

 min 



Figure 2. Showing reduction in sensitivity of rat stomach muscle preparation 

 to 5-hydroxytryptamine, following reserpinc 



rat tissues plays no part in protection of the animal against X irradiation. A 

 change to the ' free ' form gives protection, even in the presence of refractory 

 5-OHT receptors on smooth muscle cells, but more critical experimentation 

 is required and is being carried out to establish this point which is of crucial 

 importance in the mechanism of 5-OHT protection in vivo. 



Effect of 5-OHT antagonists and antimetabolites 



A range of 5-OHT analogues of proven specificity are availal)le, largely 

 owing to the researches of WooUey and Sha\v. 



Two types of tryptamine receptors are present, which can be selectively 

 blocked 20' 21 — M receptors, probably present on nerve endings and selectively 

 blocked by morphine and atropine, and D receptors present on smooth muscle 

 and selectively blocked by 5-OHT analogues and certain ^-haloalkylamines 

 {e.g. dibenzyline or phenoxybenzaminc). Of these, the latter {D receptors) 



174 



