Pretreatment with glucose increases entry of urocortin into mouse brain.
Although urocortin is a potent inhibitor of food ingestion after peripheral administration, it was recently shown that under normal conditions this peptide crosses the blood-brain barrier (BBB) at a very slow rate. We examined whether hyperglycemia could stimulate the rate of entry (K(i)) of (125)I-urocortin into the mouse brain. In euglycemic mice, (125)I-urocortin injected iv entered the brain at a rate similar to that of the vascular marker (99m)Tc-albumin. However, injection of glucose (3 g/kg, ip) 0.5, 1, or 2 h before the (125)I-urocortin greatly increased the influx of urocortin. Without the glucose, the self-inhibition characteristic of a saturable transport system was not apparent. Self-inhibition could be demonstrated after the glucose injection, indicating activation of a transport system for urocortin that was saturable. Injection of insulin (10 U/kg, ip) 1 or 2 h before the (125)I-urocortin decreased the K(i). Thus, the entry of urocortin into brain can be activated by changes in the concentration of blood glucose, illustrating the responsiveness of the BBB to regulatory influences.
Kastin
A J
AJ
VA Medical Center and Tulane University School of Medicine, New Orleans, LA 70112-1262, USA.
Akerstrom
V
V
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects* / Q000493:pharmacokinetics*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D005947:Glucose / Q000819:agonists*; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013311:Streptozocin; D054832:Urocortins
D001786:Blood Glucose; D007328:Insulin; D054832:Urocortins; D013311:Streptozocin; D003346:Corticotropin-Releasing Hormone; D005947:Glucose