Effects of histamine and 5-hydroxytryptamine on the growth rate of xenografted human bronchogenic carcinomas.

1. The influence of histamine and 5-hydroxytryptamine (5-HT) antagonists and agonists on the volume doubling times (Td) of human bronchogenic carcinomas propagated as s.c. xenografts in immunosuppressed mice was examined. 2. The H2-receptor antagonists, cimetidine and ranitidine, increased Td. 3. Treatment with the H2-receptor agonist, 4-methyl histamine, had no effect on Td. 4. Co-administration of 4-methyl histamine and cimetidine abolished the effects of cimetidine. 5. The 5-HT2-receptor antagonists, cinanserin and ketanserin, both increased Td. 6. Treatment with the 5-HT1/2-receptor agonist quipazine (0.1 mg/kg, reflecting 5-HT2 agonist activity) decreased Td, while a higher dose (10.0 mg/kg) had no effect. 7. The 5-HT1/2-receptor antagonist, methiothepin, decreased Td. 8. The 5-HT uptake inhibitor, fluoxetine, increased Td in one tumour line but not in another, while the 5-HT releaser/depletor, fenfluramine, increased Td. 9. Histamine may stimulate tumour growth through the histamine H2-receptor, while the dominant effect of 5-HT is 5-HT1-receptor inhibition. 10. Tumour growth in some bronchogenic carcinomas may involve 5-HT uptake mechanisms.