1. Some parameters of salivary secretion (latency, volume of saliva, duration of salivation and concentration and amount of histamine in the submaxillary gland and saliva) were determined after i.a. administration of pilocarpine, physostigmine, carbachol, acetylcholine, histamine and mepyramine to dogs. Dose-response relationships after i.a. and i.v. administration are presented.
2. After the injection of pilocarpine the volume of saliva is directly proportional to the amount of histamine in the submaxillary gland and, in the same dog, to the amount of histamine in the saliva. A correlation was found between the amount of histamine in saliva and the increase of activity of the specific histidine decarboxylase in the gland (adaptative formation of histamine).
3. In experiments in which attempts were made to exhaust the gland by numerous injections of pilocarpine the initial intensity of the response was diminished by only 13% after many hours, whereas the time of latency was prolonged and the duration of response was, in parallel with the histamine amount of the saliva, strongly diminished.
4. After the injections of physostigmine, the volume of saliva is directly proportional to the amount of histamine in the saliva, not only in the same dog, but also between different dogs. The latency of the response and the secretion curve contradict a direct action of physostigmine at the secreting cell.
5. In contrast to other antihistamine drugs which inhibit the salivation induced by parasympathetic drugs and histamine, mepyramine causes a large release of histamine and stimulation of salivary secretion, which could be inhibited by the former antihistamine drugs.
6. Histamine induced salivation is strongly augmented by prestimulation of the submaxillary gland with pilocarpine, carbachol, physostigmine, nicotine, and by treatment with aminoguanidine. Aminoguanidine (5 mg/kg) itself stimulates salivation. After i.a., but not after i.v. administration of histamine, the release of histamine into the saliva is increased. Injected histamine is partly stored by “glandotrop” histamine pools (pools, from which histamine is released in order to stimulate directly elements in the same gland) and can be released by pilocarpine, acetylcholine, and physostigmine. Only histamine which is released from stores is involved in the stimulation of secretion.
7. The pancreatic juice obtained by stimulation by secretin and pilocarpine, but not by pancreocymine, contains histamine in a high concentration which is constant during the whole secretion period. Histamine itself stimulates pancreatic secretion.
8. A model showing how histamine mediates parasympathetic stimulation of the submaxillary gland is discussed: acetylcholine from parasympathetic nerve endings releases histamine from the “glandotrop” histamine stores. Histamine then stimulates glandular elements.