Specific esponse to 5-HT2 agonists by arterioles linked to Meth A tumors in mice.
Using intravital microscopy, we compared the responses to serotonin [5-hydroxytryptamine (5-HT)] and to a specific 5-HT2 agonist [1-(2,5-dimethoxy-4-bromo-phenyl)-2-aminopropane (DOB)] by normal arterioles and by the host-modified arterioles feeding a Meth A tumor implanted into the flank of female BALB/c mice. Topical and intravenous administration of 5-HT (10(-6) to 10(-4) M and 0.01-10 micrograms) or DOB (5 x 10(-7) to 5 x 10(-5) M and 0.01-10 micrograms) induced arteriolar constriction, which was far more pronounced for the arterioles feeding the tumor. This larger degree of vasoconstriction in tumor-feeding vs. normal arterioles was not found with norepinephrine. We also compared tumor growth and the mouse life span in three groups of mice, which were given 1 mg of serotonin or 0.74 mg DOB or saline solution. 5-HT or DOB both reduced tumor growth drastically compared with the controls (P less than 0.001), and survival rates were significantly higher in the 5-HT or DOB-treated groups (P less than 0.001). We conclude that 5-HT2-serotoninergic agonists are of particular pharmacological interest, since their vasoconstrictive action on the microvasculature feeding the tumors is much greater than in normal tissue and may interfere with tumor growth.
Stücker
O
O
Department of Biophysics, Hôpital F. Widal, Paris, France.
Vicaut
E
E
Teisseire
B
B
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005354:Fibrosarcoma / Q000098:blood supply* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012513:Sarcoma, Experimental / Q000098:blood supply* / Q000473:pathology; D012701:Serotonin / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply
D011985:Receptors, Serotonin; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C003943:2,5-dimethoxy-4-bromoamphetamine; D012701:Serotonin; D009638:Norepinephrine