beta-Adrenergic blockade of prostaglandin E2- and D2-induced erythroid colony formation.
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.
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D002078:Butoxamine / Q000494:pharmacology*; D015232:Dinoprostone; D004347:Drug Interactions; D004920:Erythropoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology*; D013237:Stereoisomerism
D011412:Propanolamines; D011457:Prostaglandins D; D011458:Prostaglandins E; D002078:Butoxamine; D011433:Propranolol; D015232:Dinoprostone; D015230:Prostaglandin D2