title: Homeostatic role of the active transport in elimination of [3H]benzylpenicillin out of the cerebrospinal fluid system.
abstract: Cerebral acidic metabolites and penicillin are organic anions which can be carried by active transport into capillaries of the central nervous system (CNS). However, it is generally believed that these metabolites are mainly delivered from CNS to cerebrospinal fluid (CSF) and eliminated by CSF circulation over cortex and its absorption into dural venous sinuses. To test this hypothesis we studied fate of penicillin ([3H]benzylpenicillin) in the CSF under control conditions and when its active transport was blocked by probenecid. After application of penicillin into cisterna magna of control dogs, it is distributed only in traces to lumbar, ventricular and cortical CSF. However, when active transport of penicillin across capillary wall is blocked by probenecid, its disappearance from cisterna is slowed down and its distribution is greatly enhanced so that at 300 min penicillin concentrations in cisternal, lumbar and cortical CSF approach or equal each other. Disappearance of penicillin from cisternal CSF shows a single exponential course (half-time 30 min) in control, while in probenecid pretreated dogs this is a slow multiexponential process. The results indicate that the active transport across capillary wall in CNS, but not generally postulated unidirectional CSF circulation over cortex and its absorption into dural venous sinuses, is instrumental in elimination of cerebral acidic metabolites and in such a way homeostasis in brain and cerebrospinal fluid is maintained.
authors.affiliation: Department of Pharmacology, University of Zagreb School of Medicine, Croatia.
authors.forename: A
authors.initials: A
authors.lastname: Vladić
authors.forename: N
authors.initials: N
authors.lastname: Strikić
authors.forename: D
authors.initials: D
authors.lastname: Jurcić
authors.forename: M
authors.initials: M
authors.lastname: Zmajević
authors.forename: M
authors.initials: M
authors.lastname: Klarica
authors.forename: M
authors.initials: M
authors.lastname: Bulat
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D004285:Dogs; D023421:Models, Animal; D010400:Penicillin G / Q000493:pharmacokinetics*; D010406:Penicillins / Q000493:pharmacokinetics*; D011339:Probenecid / Q000494:pharmacology
chemical_list: D010406:Penicillins; D011339:Probenecid; D010400:Penicillin G