Carrier‐mediated transport of vasorpressin across the blood‐brain barrier of the mouse

Abstract

A brain to blood carrier-mediated transport system for arginine vasopressin (AVP) was investigated in mice after intraventricular injection of iodinated AVP and varying amounts of unlabeled material or candidate inhibitors. Residual activity in the brain detected after decapitation was used as the main determinant of transport activity. The half-time disappearance of iodinated AVP from the brain was 12.4 min, the Vmax was 1.41 nmol/g-min, and the apparent Km was 28.7 nmol/g. A 30-nmol dose of AVP, mesotocin, arginine vasotocin, pressinoic amide, pressinoic acid, tocinoic acid, and lysine vasotocin, but not oxytocin, lysine vasopressin, AVP free acid, tocinoic amide, Tyr-MIF-1, or cyclo Leu-Gly, significantly (P less than 0.05) inhibited the transport of iodinated AVP out of the brain. The 30 nmol dose of AVP had no effect on the transport of iodide or iodotyrosine out of the brain. High-performance liquid chromatography showed that 59.2% of the radioactivity found in the blood 2 min after an i.c.v. injection of labeled AVP eluted at the same position as labeled AVP compared with 68.8% of radioactivity eluting at that position after material was infused i.v. for 2 min. This indicates that intact peptide is transported across the blood-brain barrier and that most of the degradation of AVP occurs during circulation in the blood. Calculations based on the appearance of radioactivity in the periphery showed that 56.2% of the material injected centrally would have been transported into the periphery by 10 min. This appearance of material in the periphery was inhibited by the simultaneous injection of an excess of unlabeled peptide. Water loading significantly decreased the brain to blood transport rate of AVP by 40%. It is concluded that a saturable system exists for brain to blood transport of AVP and some structurally similar peptides.

Endomorphins, Met-Enkephalin, Tyr-MIF-1, and the P-glycoprotein Efflux System

“…The system has been verified by measurement of intact Tyr-MIF-1 and vasopressin in blood after i.c.v. administration (Banks et al, 1987(Banks et al, , 1990, and an excellent correlation for several substances exists between the rate of disappearance from brain and the rate of appearance in blood (Banks and Kastin, 1992). The method accurately quantifies efflux, unlike some other methods that measure efflux only as an index.…”

Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger's Disorders

“…Early studies seemed to indicate that oxytocin and vasopressin, or at least physiologically significant amounts of these peptides, are excluded access to most regions of the CNS by the blood-brain barrier (BBB) (Ermisch et al, 1988;Meisenberg and Simmons, 1983b). However, more recently, a bidirectional saturable active transport mechanism across the BBB has been demonstrated for vasopressin (Banks et al, 1987;Zlokovic et al, 1990). The behavioral effects of peripherally circulating peptides may be indirect such as via the alteration of the BBB permeability to other substances.…”

Unidirectional Specific and Modulated Brain to Blood Transport of Corticotropin-Releasing Hormone

“…hCRH and oCRH were rapidly transported out of the brain, the half-time disappearances from the CNS being roughly half those in the vascular space and as low as those reported for some other peptides such as vasopres sin, in which rapid clearance by a specific transport sys tem has been described [21]. This rapid efflux out of the brain cannot be accounted for by the reabsorption of the cerebrospinal fluid, which is a much slower process [42].…”