AJP - Cell Physiology, Vol 245, Issue 5 322-C327, Copyright © 1983 by American Physiological Society
beta-Adrenergic blockade of prostaglandin E2- and D2-induced erythroid colony formation
M. Belegu, B. Beckman and J. W. Fisher
beta-Adrenergic receptors have been linked to the actions of
beta-adrenergic agonists as well as that of other hormones on erythroid
cells. In the present studies, arachidonic acid, the precursor for the
endoperoxide intermediates for prostaglandins, was demonstrated to produce
a significant increase in erythroid colony (CFU-E) formation in normal
mouse bone marrow cultures. Meclofenamate, a cyclooxygenase inhibitor drug
that inhibits prostaglandins synthesis, significantly inhibited the
increase in CFU-E colony-forming cells produced by arachidonic acid, thus
establishing that arachidonic acid was probably converted to some
prostaglandin or prostaglandin metabolite in the bone marrow to trigger
CFU-E. Prostaglandins E2 (PGE2) and D2 (PGD2), both of which have been
demonstrated to be produced in the bone marrow, were found in the present
studies to increase the number of CFU-E colonies in normal mouse bone
marrow cultures. DL-Propranolol, a beta 1, beta 2-adrenergic blocking
agent, and D-propranolol, a non-beta-blocking isomer with nonspecific
membrane stabilizing effects, both produced a significant (P less than
0.01) inhibition of the effects of PGE2 or PGD2 on CFU-E in murine bone
marrow cultures. Butoxamine, a somewhat selective beta 2-adrenergic
antagonist drug, also produced a significant inhibition of the effects of
PGE2 on CFU-E in murine marrow cultures. These results indicate that the
effects of beta-adrenergic blocking agents on prostaglandin-stimulated
CFU-E are due to their membrane-stabilizing action rather than specific
beta-adrenergic blockade.
