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Am J Physiol Endocrinol Metab 260: E633-E640, 1991;
0193-1849/91 $5.00
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AJP - Endocrinology and Metabolism, Vol 260, Issue 4 E633-E640, Copyright © 1991 by American Physiological Society

ARTICLES

Vasopressin uptake by hypothalamopituitary axis and pineal gland in guinea pigs

B. V. Zlokovic, S. Hyman, J. G. McComb, G. Tang, A. R. Rezai and M. H. Weiss
Division of Neurosurgery, Children's Hospital of Los Angeles, California.

The uptake of circulating arginine vasopressin (AVP) by the pituitary gland (anterior lobe), pineal gland, and hypothalamus (ventromedial part) was investigated in an isolated in situ perused brain of anesthetized guinea pig. Kinetic experiments revealed saturable AVP uptake in all studied regions with Km values of 0.79, 0.19, and 0.76 microM and maximum velocity values of 22, 2.1, and 1.6 pmol.min-1.g-1 for the pituitary gland, pineal gland, and hypothalamus, respectively. The nonsaturable components (diffusion constants) were not significantly different from zero. Peptide fragments, L-phenylalanine, and Bestatin (an aminopeptidase inhibitor) did not interfere with AVP uptake. However, uptake of AVP was strongly inhibited in the presence of the V1 antagonist [1-(beta-mercapto-beta-beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]AVP at 2.7 microM, and regional Ki values, assuming that the observed inhibitions were purely competitive, ranged between 0.32 and 2.23 microM. The V2 agonist 1-desamino-8-D-AVP at 2.7 microM produced only a weak inhibition of AVP uptake, and regional Ki values ranged between 9.56 and 21.3 microM. It is concluded that specific uptake mechanisms in the hypothalamopituitary axis and pineal gland are sensitive enough to detect blood-borne AVP under the physiological hormonal state. It is suggested that AVP binding in situ is primarily related to V1 receptors, which may be involved in mediating the central effects of this circulating peptide.


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