Chapter XI 



THE EFFECTS OF A SPECIFIC HISTAMINE-LIBERATOR, 

 COMPOUND 48 80, ON THE MAST CELLS OF THE RAT 



{See Riley and West, \955a) 



THE original demonstration that mast cells store and release histamine, 

 described in Chapter VIII, involved the use of rather toxic chemicals, 

 some of which {e.g. stilbamidine, d-tubocurarine) have pharmacological 

 actions which are unconnected with the release of histamine. It was therefore 

 difficult to be certain that the disruption of the mast cells reflected only the 

 release of histamine. The toxicity of these compounds also precluded prolonged 

 study of their effects. 



However, there is now available a more specific and a less toxic histamine- 

 liberator, compound 48 80 (Paton, 1951 ; Paton and Schachter, 1951 ; Feldberg 

 and Miles, 1953; Feldberg and Talesnik, 1953). This substance, a condensation 

 product of p-methoxyphenethylmethlyamine and formaldehyde, was therefore 

 used in a further study of the tissue changes in three groups of rats subjected to 

 intraperitoneal injection of compound 48 80, (1) for one day only — 'acute 

 dosage', (2) for five days — 'subacute dosage', and (3) for thirty-one days — 

 'chronic dosage'. In addition there was a fourth group in which the drug was 

 injected intra-arterially to allow study of a localized area of effect. For this 

 the ear was chosen, since the ear in the rat has a very high content of mast 

 cells. At selected times in each experiment appropriate tissues were taken for 

 histamine assay and microscopical study of the mast cells. 



The present work shows that a tissue depleted of its histamine by this 

 histamine-liberator is devoid of mast cells and that the recovery or return of 

 the mast cells is accompanied by a reappearance of assayable histamine. The 

 long-term experiments confirm that compound 48/80 is toxic to the rat only by 

 virtue of its ability to release histamine : it is thus a specific histamine-liberator 

 for this species. 



Materials and methods 



Animals. In all, 170 young male rats (wt. 90-110 g.) of the Wistar strain 

 were used. To obtain representative initial values of the histamine content 

 of tissues, four control groups of six rats were killed by a blow on the head, 

 and pooled tissues from each group were assayed. The experimental animals 

 were killed in groups of seven, as follows: 'Acute dosage' expt., at days 



93 



