Changes in Sensitivity to Chemical Stimuli 1 1 1 



glionic neurone, revealed by a supersensitivity when the fibres 

 are removed or prevented from acting by means of an antagonistic 

 drug, does not manifest itself in secretion. A further argument 

 may be that the activity of the secretory mechanism which appears 

 as a spontaneous secretion, not elicited via the receptors, is not 

 affected by denervation and whereas a more or less continuous 

 activity evoked over a long period by injected agents such as 

 pilocarpine prevents the development of the denervation super- 

 sensitivity, the spontaneous secretion lacks that effect (Emmelin 

 1953a). It should be kept in mind, on the other hand, that the 

 sensitization is non-specific. When the gland cell is deprived of 

 the action of acetylcholine, for instance, it becomes supersensitive 

 not only to acetylcholine but to adrenaline as well. The sensitiza- 

 tion process, therefore, does not seem to take place in that part 

 of the mechanism activating the secretory machinery which is 

 responsible for the specificity of action of the stimulating agents 

 and where the specific antagonists work. 



The next problem concerns the nature of the changes in the 

 receptor region which occur when the impingement of transmit- 

 ters is reduced or abolished and no related agents, able to react with 

 the receptors like the transmitters, are administered. These changes 

 develop gradually to reach their maximum after two or three weeks. 

 They are reversible ; when pilocarpine is administered to a dener- 

 vated gland, or a long-lasting treatment of a normal gland with a 

 parasympathicolytic agent is discontinued, normal conditions are 

 restored within a few days. No connection has so far been detected 

 between the changes responsible for the supersensitivity and 

 changes seen in the microscope after denervation. More attention 

 has been paid to the chemical alterations which take place in the 

 gland when nerves are cut; in particular, changes in the activity 

 of enzymes which limit the action of secretory agents have been 

 studied. The "enzyme hypothesis" applied to the salivary glands 

 has been discussed by Stromblad (1956J, 19576), who estimated 

 the sensitivity to different drugs, and the activity of cholinesterase 

 and amine oxidase, after denervation and after treatment with 

 pilocarpine or an atropine-like drug; further, he made comparisons 

 between the secretory responses after denervation and after acute 

 administration of anticholinesterases. From this work it is apparent 

 that there is as yet no general, clear-cut relation between sensitiza- 

 tion and activity of the enzymes studied. There are some suggestive 



