Beta-adrenergic agonists regulate cell membrane fluctuations of human erythrocytes.
1. Mechanical fluctuations of the cell membrane (CMFs) in human erythrocytes reflect the bending deformability of the membrane-skeleton complex. These fluctuations were monitored by time-dependent light scattering from a small area ( approximately 0. 25 microm2) of the cell surface by a method based on point dark field microscopy. 2. Exposure of red blood cells (RBCs) to adrenaline (epinephrine) and isoproterenol (isoprenaline) resulted in up to a 45 % increase in the maximal fluctuation amplitude and up to a 35 % increase in the half-width of the amplitude distribution. The power spectra of membrane fluctuations of control and treated cells revealed that adrenaline stimulated only the low frequency component (0.3-3 Hz). Analysis of the dose-response curves of beta-adrenergic agonists yielded an EC50 of 5 x 10-9 and 1 x 10-11 M for adrenaline and isoproterenol, respectively. Propranolol had an inhibitory effect on the stimulatory effect of isoproterenol. These findings show a potency order of propranolol > isoproterenol > adrenaline. 3. The stimulatory effect of adrenaline was a temporal one, reaching its maximal level after 20-30 min but being abolished after 60 min. However, in the presence of 3-isobutyl-1-methylxanthine, a partial stimulatory effect was maintained even after 60 min. Pentoxifylline and 8-bromo-cAMP elevated CMFs. However, exposure of ATP-depleted erythrocytes to adrenaline or 8-bromo-cAMP did not yield any elevation in CMFs. These findings suggest that the beta-agonist effect on CMFs is transduced via a cAMP-dependent pathway. 4. Deoxygenation decreased CMFs and filterability of erythrocytes by approximately 30 %. The stimulatory effect of isoproterenol on CMFs was 2.2-fold higher in deoxygenated RBCs than in oxygenated cells. 5. Exposure of RBCs to adrenaline resulted in a concentration-dependent increase in RBC filterability, demonstrating a linear relationship between CMFs and filterability, under the same exposure conditions to adrenaline. These findings suggest that beta-adrenergic agonists may improve passage of erythrocytes through microvasculature, enhancing oxygen delivery to tissues, especially under situations of reduced oxygen tension for periods longer than 20 min.
Tuvia
S
S
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, 69978 Tel-Aviv, Israel.
Moses
A
A
Gulayev
N
N
Levin
S
S
Korenstein
R
R
D000255:Adenosine Triphosphate / Q000097:blood; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004912:Erythrocytes / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008027:Light; D008729:Methoxamine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D012542:Scattering, Radiation; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D008729:Methoxamine; D007545:Isoproterenol; D010100:Oxygen; D004837:Epinephrine