© 1998 American Heart Association, Inc.
Original Contributions |
1-Adrenergic Stimulation of Sarcolemmal Na+-H+ Exchanger Activity in Rat Ventricular Myocytes
Evidence for Selective Mediation by the 1A-Adrenoceptor Subtype
From Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London, UK.
Correspondence to Dr Metin Avkiran, Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, Lambeth Palace Rd, London SE1 7EH, UK. E-mail m.avkiran{at}umds.ac.uk
Abstract—1-Adrenoceptor
(1-AR) stimulation increases sarcolemmal
Na+-H+ exchanger (NHE) activity. The
present study was designed to determine the role(s) of
1-AR subtype(s) in mediating this response. As an index
of NHE activity, acid efflux rates (JHs)
were determined in single rat ventricular myocytes loaded
with the pH-sensitive fluoroprobe carboxy-seminaphthorhodafluor-1 after
2 consecutive intracellular acid pulses in bicarbonate-free medium.
JH at pHi 6.90 did not change
significantly during the second pulse relative to the first in control
cells but increased in a dose-dependent manner when the second pulse
occurred in the presence of phenylephrine (nonselective
1-AR agonist) or A61603 (1A-AR–selective
agonist), with EC50 values of 1.24 µmol/L and 3.6
nmol/L, respectively (both agonists given together with 1 µmol/L
atenolol). Stimulation of NHE activity by 10 µmol/L
phenylephrine was inhibited in a dose-dependent manner by
the competitive antagonists prazosin, WB4101, and
5-methylurapidil, with IC50 values of 12, 32, and 149
nmol/L, respectively. Analyses of the relative EC50
and IC50 values obtained (and Ki
values estimated from the antagonist IC50s) in relation to
the relative potencies of these agents at native rat
1-AR subtypes and their relative affinities for
recombinant rat 1-ARs suggest that
1-adrenergic stimulation of sarcolemmal NHE activity is
likely to be mediated selectively by the 1A-AR.
Key Words: Na+-H+ exchanger • 1-adrenoceptor subtype • myocyte • receptor selectivity
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