Extra- and intracellular signaling pathways under red blood cell aggregation and deformability changes.
Exposure of red blood cells (RBCs) to catecholamines (epinephrine, phenylephrine, an agonist of alpha1-adrenergic receptors, clonidine, an agonist of alpha2-adrenergic receptors and isoproterenol, an agonist of beta-adrenergic receptors) led to change in the RBC microrheological properties. When forskolin (10 microM), an AC stimulator was added to RBC suspension, the RBC deformability (RBCD) was increased by 17% (p<0.05). Somewhat more significant deformability rise appeared after RBC incubation with dB-AMP (by 27%; p<0.01). Red blood cell aggregation (RBCA) was significantly decreased under these conditions (p<0.01). All drugs having PDE activity increased red cell deformability similarly. Some more changes of deformability was found after RBC incubation with pentoxifylline--25% (p<0.05) and IBMX incubation was accompanied only by 15% rise of RBC deformability. The drugs with PDE inhibitory activity reduced red cell aggregation. The most significant RBCA reduction effect was found under cell incubation with pentoxifylline and inhibitor PDE1-vinpocetine. On the whole RBCA reduction averaged 36% (p<0.05) under RBCs incubation with PDE inhibitors. The rise of Ca2+ influx, stimulated by A23187, was accompanied by an increase of RBCA, whereas red cell deformability was changed insignificantly. At the same time Ca2+ entry blocking into the red cells by verapamil or its chelating in medium by EGTA led to significant RBCA decrease and deformability rise (p<0.05).On the whole the total data clearly show that the red cell aggregation and deformation changes were connected with an activation of the different intracellular signaling pathways. It seems reasonable to suppose that RBCA decrease was mainly associated with an activation of the adenylyl-cyclase-cAMP system, while the red cell deformability was closely associated with Ca2+ control mechanisms.
Muravyov
Alexei V
AV
Department of Medicine and Biology, University of Yaroslavl, 150000 Yaroslavl, Russia. alexei.47@mail.ru
Tikhomirova
Irina A
IA
Maimistova
Alla A
AA
Bulaeva
Svetlana V
SV
D000262:Adenylyl Cyclases / Q000097:blood; D000328:Adult; D002395:Catecholamines / Q000494:pharmacology*; D004903:Erythrocyte Aggregation / Q000187:drug effects / Q000502:physiology*; D004907:Erythrocyte Deformability / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D018056:Hemorheology / Q000187:drug effects; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
D002395:Catecholamines; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases