Antipyretic doses of centrally administered vasopressin reach physiologically meaningful concentrations in the brain of the rat as evaluated by microdialysis.
It was important to determine whether vasopressin (AVP) injected intracerebroventricularly (i.c.v.) in the rat reached the site of action within the ventral septal area (VSA) in sufficient concentrations to account for its physiological effects. Microdialysis was used to evaluate this hypothesis. The exchange rate across the dialysis tubing was determined in vitro to be 0.40%. After placement of the microdialysis cannula in the VSA of the rat the recovery of i.c.v. injected labelled or cold AVP was 0.23 and 0.20%, respectively. Maximum concentrations of AVP in the extracellular fluid of the VSA was determined to be 10.7 nM after 10 ng i.c.v. and hence extrapolated to be 1.07 nM after 1 ng i.c.v. or 2.65 nM after 2.5 ng i.c.v. between which lies the threshold dose of AVP for its antipyretic effects. This can be compared with a reported Kd for these receptors of 1.06 nM as determined by receptor binding assay.
Kasting
N W
NW
Department of Physiology, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Wilkinson
M F
MF
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001127:Arginine Vasopressin / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes; D008297:Male; D008832:Microchemistry; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007457:Iodine Radioisotopes; D014667:Vasopressins; D001127:Arginine Vasopressin