Effect of histamine on the blood-tumor barrier in transplanted rat brain tumors.
We studied the effect of intracarotid administration of histamine on the blood-tumor barrier permeability and also on the blood-brain barrier permeability in transplanted rat C6 glioma. There was no definite Evans blue (EB) extravasation either in normal or tumor tissue after intracarotid saline infusion. In contrast, histamine at doses of 1 and 10 micrograms/kg/min produced slight to moderate EB extravasation in the tumor without any significant extravasation in the normal brain tissue. Intravenously administered H1 and H2 receptor antagonists (5 mg/kg each) reduced the histamine (10 micrograms/kg/min) induced extravasation of EB in the tumor tissue. These results indicated that brain tumor vessels responded to histamine in a different fashion from normal brain capillaries. Histamine could thus be utilized for selective drug delivery to brain tumors without affecting normal brain tissue.
Nomura
T
T
Department of Neurosurgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ikezaki
K
K
Matsukado
K
K
Fukui
M
M
D000818:Animals; D001479:Basal Ganglia / Q000098:blood supply / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001929:Brain Edema / Q000473:pathology*; D001932:Brain Neoplasms / Q000098:blood supply* / Q000473:pathology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000473:pathology; D005910:Glioma / Q000098:blood supply* / Q000473:pathology; D006632:Histamine / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
D005070:Evans Blue; D006632:Histamine