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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Beta 2-adrenergic receptor and angiotensin II receptor modulation of sympathetic neurotransmission in human atria.

The aim of the present study was to investigate beta-adrenergic receptor and angiotensin II (Ang II) receptor modulation of norepinephrine release in human atria. Slices of human atrial appendages were incubated with [3H]norepinephrine, superfused with Krebs-Henseleit solution, and electrically stimulated in superfusion chambers. Pretreatment of the tissue with 6-hydroxydopamine (1.2 mmol/L) before the [3H]norepinephrine incubation to destroy sympathetic nerves reduced the uptake of radioactivity and abolished the stimulation-induced (S-I) outflow of radioactivity. Furthermore, S-I outflow of radioactivity was prevented by the addition of tetrodotoxin (1 mumol/L) to and omission of extracellular Ca2+ from the superfusion solution. Separation of [3H]norepinephrine from its metabolites revealed that the S-I outflow of radioactivity was mainly composed of intact [3H]norepinephrine. Thus, the S-I outflow of radioactivity was taken as an index of norepinephrine release. Isoproterenol (0.001 to 0.1 mumol/L) dose-dependently enhanced the S-I outflow of radioactivity. The concentration-response curve of isoproterenol was shifted to the right by the selective beta 2-adrenergic receptor antagonist ICI 118551 (0.01 and 0.1 mumol/L) but not by the beta 1-adrenergic receptor-selective antagonist atenolol (0.3 and 30 mumol/L). Ang II (0.001 to 1.0 mumol/L) also dose-dependently enhanced S-I outflow of radioactivity. The facilitatory effect of Ang II was blocked by either the peptide Ang II receptor antagonist saralasin (1.0 mumol/L) or EXP 3174 (0.1 mumol/L), the in vitro active form of the nonpeptide Ang II receptor antagonist losartan. The cell-permeable cAMP analogue 8-bromo-cAMP (30 to 300 mumol/L) dose-dependently enhanced S-I outflow of radioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

References

  1. Beta 2-adrenergic receptor and angiotensin II receptor modulation of sympathetic neurotransmission in human atria. Rump, L.C., Schwertfeger, E., Schaible, U., Fraedrich, G., Schollmeyer, P. Circ. Res. (1994) [Pubmed]
 
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