title: Transport, uptake, and metabolism of blood-borne vasopressin by the blood-brain barrier.
abstract: Transport, binding, and metabolism of [phenylalanyl-3,4,5,-3H(N)]arginine vasopressin (AVP) by the blood-brain barrier (BBB) was studied in adult guinea-pigs by means of a novel vascular brain perfusion (VBP)/capillary depletion technique and HPLC. A time-dependent, progressive brain uptake of 3H-radioactivity was measured over the 10 min period of VBP both in brain homogenates and in brain tissue depleted of cerebral microvessels. The unidirectional blood-to-brain transport constant, K(IN), estimated by multiple-time tissue uptake analysis of the homogenate and postcapillary supernatant, indicated that the BBB transfer rate for [3H]AVP (K(IN) = 2.37 +/- 0.25 microliters min-1 per gram brain homogenate) was almost 10 times higher than for simultaneously perfused [14C]sucrose, a cerebrovascular space marker. In contrast to homogenate and postcapillary supernatant, the [3H]radioactivity determined in the vascular pellet after dextran density centrifugation of the brain homogenate was very low and only somewhat higher than for [14C]sucrose. HPLC analysis of the perfused brain tissue revealed time-dependent degradation of the blood-borne neuropeptide. The percentage of intact [3H]AVP as determined in the postcapillary supernatant progressively declined during brain perfusion, from 49% at 1 min to 11.9% at 10 min. The major detectable labeled metabolite was [3H]phenylalanine, the labeled amino acid residue of [3H]AVP. The aminopeptidase inhibitor bestatin (0.5 mM), perfused simultaneously with [3H]AVP by the VBP technique, did not alter tissue uptake of [3H]AVP, indicating that there was no significant hydrolysis of peptide by the luminal BBB surface.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Neurological Surgery, Childrens Hospital Los Angeles, University of Southern California.
authors.forename: B V
authors.initials: BV
authors.lastname: Zlokovic
authors.forename: W A
authors.initials: WA
authors.lastname: Banks
authors.forename: H
authors.initials: H
authors.lastname: el Kadi
authors.forename: J
authors.initials: J
authors.lastname: Erchegyi
authors.forename: J B
authors.initials: JB
authors.lastname: Mackic
authors.forename: J G
authors.initials: JG
authors.lastname: McComb
authors.forename: A J
authors.initials: AJ
authors.lastname: Kastin
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood* / Q000493:pharmacokinetics; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006168:Guinea Pigs; D008297:Male; D010477:Perfusion; D011485:Protein Binding; D012588:Scintillation Counting
chemical_list: D001127:Arginine Vasopressin