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Vol. 58, Issue 5, 1075-1084, November 2000
Institute of Cell Signalling and School of Biomedical Sciences,
Medical School, Queen's Medical Centre, Nottingham, United Kingdom
Activation of A1 adenosine receptors leads to the
inhibition of cAMP accumulation and the stimulation of inositol
phosphate accumulation via pertussis toxin-sensitive G-proteins. In
this study we have investigated the signaling of the A1
adenosine receptor in Chinese hamster ovary (CHO) cells, when
expressed at approximately 203 fmol/mg (CHOA1L) and at approximately
3350 fmol/mg (CHOA1H). In CHOA1L cells, the agonists
N6-cyclopentyladenosine (CPA),
(R)-N6-(2-phenylisopropyl)adenosine,
and 5'-(N-ethylcarboxamido)adenosine (NECA) inhibited
cAMP production in a concentration-dependent manner. After
pertussis toxin treatment, the agonist NECA produced a stimulation of
cAMP production, whereas CPA and
(R)-N6-(2-phenylisopropyl)adenosine
were ineffective. In CHOAIH cells, however, all three agonists produced
both an inhibition of adenylyl cyclase and a pertussis
toxin-insensitive stimulation of adenylyl cyclase. All three agonists
were more potent at inhibiting adenylyl cyclase in CHOA1H cells than in
CHOA1L cells. In contrast, A1 agonists (and particularly
NECA) were less potent at stimulating inositol phosphate accumulation
in CHOA1H cells than in CHOA1L cells. After pertussis toxin treatment,
agonist-stimulated inositol phosphate accumulation was reduced in
CHOA1H cells and abolished in CHOA1L cells. The relative intrinsic
activity of NECA in stimulating inositol phosphate accumulation,
compared to CPA (100%), was much greater in the presence of pertussis
toxin (289.6%) than in the absence of pertussis toxin (155.2%). These
data suggest that A1 adenosine receptors can couple to both
pertussis toxin-sensitive and -insensitive G-proteins in an expression
level-dependent manner. These data also suggest that the ability of
this receptor to activate different G-proteins is dependent on the
agonist present.
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