Dopaminergic regulation of granulocytopoiesis during cytostatic-induced myelosuppressions.
The role of the dopaminergic system in the regulation of the granulocytic hemopoietic stem was studied after administration of cyclophosphamide and 5-fluorouracil. Dopamine in the central nervous system promotes the development of cytostatic-induced myelosuppressions. The inhibitory effect of dopaminergic structures on granulocytopoiesis after administration the fluoropyrimidine antimetabolite was of shorter duration compared to that observed in experiments with the alkylating agent. The inhibitory effect of brain dopamine is associated with a decrease in proliferative activity and differentiation of granulomonocytic precursors, prevention of hemopoietic islet formation, and impairment of secretion of colony-stimulating activity in adherent cells of the hemopoiesis-inducing microenvironment. Cyclophosphamide and 5-fluorouracil had different effects on the rate of hemopoietic tissue regeneration, which was related to specific interaction between distant regulatory structures and hemopoiesis-inducing microenvironment and differences in the influence of cytostatics on hemopoietic and stromal cells.
Skurikhin
E G
EG
Institute of Pharmacology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences.
Minakova
M Y
MY
Pershina
O V
OV
Dygai
A M
AM
Goldberg
E D
ED
D000818:Animals; D001921:Brain / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology; D054697:Cytostatic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D019653:Myeloablative Agonists / Q000494:pharmacology*
D054697:Cytostatic Agents; D018492:Dopamine Antagonists; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D006220:Haloperidol; D005472:Fluorouracil; D004298:Dopamine