AJP - Endocrinology and Metabolism, Vol 243, Issue 6 499-E504, Copyright © 1982 by American Physiological Society
Interaction between amrinone and parathyroid hormone on bone in culture
N. S. Krieger and P. H. Stern
The cardiotonic agent amrinone has been postulated to directly affect Na-Ca
exchange. Because stimulated bone resorption has been proposed to require
Na-Ca exchange, we examined the effects of amrinone on bone. Amrinone
inhibited release of Ca from neonatal mouse calvaria in organ culture
stimulated by parathyroid hormone (PTH), 1,25-dihydroxyvitamin d3, or
prostaglandin E2. Inhibition was dose dependent and maximal at 2 X 10(-4)
M. The effect of amrinone differed from the inhibitory effects of
calcitonin, ouabain, or nigericin in that 1) 6-h exposure to amrinone alone
prevented the effect of subsequently added PTH; 2) amrinone was only
partially effective if added after resorption was initiated by 24-h
treatment with PTH; 3) coincubation with amrinone and PTH during the first
48 h of culture allowed for a response to PTH after amrinone was removed;
no such protection by a stimulator occurred with ouabain or nigericin. Also
submaximal concentrations of amrinone plus calcitonin, ouabain, or
nigericin gave greater than additive inhibition of Ca release. Amrinone had
no effect on basal bone cAMP or on the acute stimulation of cAMP by PTH.
The results suggest that amrinone could have a more direct interaction with
the pathway involved in stimulated bone resorption than the other
inhibitors.
