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.
Sheehan
P F
PF
Department of Anatomy, Monash University, Clayton, Victoria, Australia.
Baker
T
T
Tutton
P J
PJ
Barkla
D H
DH
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001984:Bronchial Neoplasms / Q000473:pathology*; D002283:Carcinoma, Bronchogenic / Q000473:pathology*; D005260:Female; D018494:Histamine Agents / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014183:Transplantation, Heterologous / Q000502:physiology*
D018494:Histamine Agents; D017442:Histamine Agonists; D006635:Histamine H2 Antagonists; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors