Megakaryocytopoiesis in culture: modulation by cholinergic mechanisms.
Treatment of murine bone marrow cultures with the cholinergic agonist carbamylcholine enhanced megakaryocytic colony growth by as much as 65%. In contrast, adrenergic agonists had no such effect. Addition to cultures of dibutyryl cyclic GMP (db-cGMP) also enhanced megakaryocytic colonies up to 50%, whereas dibutyryl cyclic AMP (db-cAMP) had no effect. Sodium nitroprusside and sodium nitrite, putative guanyl cyclase activators, also enhanced colony numbers, as did imidazole, a postulated cGMP phosphodiesterase inhibitor. Preincubation of marrow for two hours with carbamylcholine resulted both an increase in colony numbers (58%) and percent of progenitors in DNA synthesis (48%, compared to 14% for controls) as determined by tritiated thymidine suicide studies. Treatment of mice with the acetylcholinesterase inhibitor neostigmine resulted in an increase in CFU-M/humerus (62%) and percent in DNA synthesis (45%). These data indicate that 1) cholinergic, but not adrenergic, agonists modulate megakaryocytopoiesis in culture; 2) this effect may be mediated by cyclic GMP; and 3) only a brief period of exposure of marrow cells to agonist results in enhancement of megakaryocytic colonies.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells; D003994:Bucladesine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000033:anatomy & histology; D009388:Neostigmine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D009599:Nitroprusside; D003995:Dibutyryl Cyclic GMP; D009388:Neostigmine; D003994:Bucladesine; D002217:Carbachol; D012977:Sodium Nitrite