Mechanism of the reduced elimination clearance of benzylpenicillin from cerebrospinal fluid in rats with intracisternal administration of lipopolysaccharide.
The mechanism responsible for the reduced clearance of benzylpenicillin (BPC) from the cerebrospinal fluid (CSF) was investigated in rats that received an intracisternal administration of lipopolysaccharide (LPS). BPC was intraventricularly injected and its elimination from the CSF studied. During the inflammation created by the LPS administration to the cisterna magna, the clearance of BPC and taurine from the CSF was significantly reduced but reverted to the control level when N-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, was intracisternally administered. The in vitro uptake of BPC and taurine was significantly reduced in the choroid plexus (CP, the blood-CSF barrier) of rats with experimental inflammation and in control CP that had been pretreated with sodium nitroprusside (SNP, an NO donor). Interestingly, the clearance and CP uptake of formycin B, a substrate for a nucleoside transporter, were not affected by the experimental inflammation or by pretreatement with SNP. These observations suggest that the BPC transporter, and probably other transport systems as well, is functionally sensitive to NO in the blood-CSF barrier. Therefore, functional impairment of BPC transport in the CP by NO may be partly responsible for the increase in BPC concentration in the CSF during inflammation such as that caused by meningitis.
Han
Hee
H
Department of Pharmaceutics, College of Pharmacy, Seoul National University, Kwanak-gu, Korea.
Kim
Sang-Geon
SG
Lee
Myung-Gull
MG
Shim
Chang-Koo
CK
Chung
Suk-Jae
SJ
D000465:Algorithms; D000818:Animals; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000166:cytology; D002831:Choroid Plexus / Q000378:metabolism; D002946:Cisterna Magna; D005573:Formycins / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009569:Nitric Oxide / Q000134:cerebrospinal fluid; D009589:Nitrogen Oxides / Q000134:cerebrospinal fluid; D010400:Penicillin G / Q000134:cerebrospinal fluid*; D010406:Penicillins / Q000134:cerebrospinal fluid*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000378:metabolism
D005573:Formycins; D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; D010406:Penicillins; C034561:formycin B; D013654:Taurine; D009569:Nitric Oxide; D010400:Penicillin G