Evidence for an A2 adenosine receptor in guinea pig lung
Naunyn Schmiedebergs Arch Pharmacol, 331 (1):
89-95 (October 1985)Ukena, D Schirren, C G Klotz, K N Schwabe, U In Vitro Germany, west
Naunyn-Schmiedeberg's archives of pharmacology Naunyn Schmiedebergs
Arch Pharmacol. 1985 Oct;331(1):89-95..Abstract
Adenosine receptors in guinea pig lung were characterized by measurement
of cyclic AMP formation and radioligand binding. 5'-N-Ethylcarboxamidoadenosine
(NECA) increased cyclic AMP levels in lung slices about 4-fold over
basal values with an EC50 of 0.32 mumol/l. N6-R-(-)-Phenylisopropyladenosine
(R-PIA) was 5-fold less potent than NECA. 5'-N-Methylcarboxamidoadenosine
(MECA) and 2-chloroadenosine had EC50-values of 0.29 and 2.6 mumol/l,
whereas adenosine and inosine had no effect. The adenosine receptors
in guinea pig lung can therefore be classified as A2 receptors. Several
xanthine derivatives antagonized the NECA-induced increase in cyclic
AMP levels. 1,3-Diethyl-8-phenylxanthine (DPX; Ki 0.14 mumol/l) was
the most potent analogue, followed by 8-phenyltheophylline (Ki 0.55
mumol/l), 3-isobutyl-1-methylxanthine (IBMX; Ki 2.9 mumol/l) and
theophylline (Ki 8.1 mumol/l). In contrast, enprofylline (1 mmol/l)
enhanced basal and NECA-stimulated cyclic AMP formation. In addition,
we attempted to characterize these receptors in binding studies with
3H NECA. The KD for 3HNECA was 0.25 mumol/l and the maximal number
of binding sites was 12 pmol/mg protein. In competition experiments
MECA (Ki 0.14 mumol/l) was the most potent inhibitor of 3HNECA
binding, followed by NECA (Ki 0.19 mumol/l) and 2-chloroadenosine
(Ki 1.4 mumol/l). These results correlate well with the EC50-values
for cyclic AMP formation in lung slices. However, the Ki-values of
R-PIA and theophylline were 240 and 270 mumol/l, and DPX and 8-phenyltheophylline
did not compete for 3H NECA binding sites. Therefore, a complete
characterization of A2 adenosine receptors by 3HNECA binding was
not achieved.(ABSTRACT TRUNCATED AT 250 WORDS)