1. The relaxant and spasmogenic effects of
purines and analogues were studied in longitudinal strips of rat gastric fundus to characterize the
purinoceptors involved. Classification was studied by use of agonist potency orders and of antagonists in circumstances where the influence of confounding factors was reduced. In general tone was raised by
carbachol (0.1 microM). 2.
Adenosine produced relaxation and was potentiated by nitrobenzylthioinosine (
NBTI, 0.3 and 30 microM), an
adenosine-uptake inhibitor. 8-Sulphophenyl-theophylline (8-SPT, 30 microM), a selective P1-purinoceptor antagonist, antagonized
adenosine and
5'-N-ethylcarboxamidoadenosine (
NECA), a selective agonist at P1-purinoceptors. 3. At resting tone,
adenosine 5'-triphosphate (
ATP) induced a small, phasic relaxation followed by a maintained
spasm. When tone was raised by
carbachol,
ATP induced a larger relaxation followed by a smaller
spasm.
NBTI did not potentiate
ATP, nor did 8-SPT antagonize
ATP, suggesting that
ATP does not act directly or indirectly at P1-purinoceptors. 4. With raised tone, and in the presence of
indomethacin (10 microM) and 8-SPT (30 microM), 2-methylthio
ATP (2-MeSATP) and
ATP produced relaxations followed by
spasms while
alpha,beta-methylene ATP (
alpha,beta-MeATP) induced only relaxation; all responses were concentration-dependent. The compounds had similar slopes and maxima for relaxation and
spasm. The rank orders of potency were
2-MeSATP much greater than
alpha,beta-MeATP greater than
ATP for relaxation and
2-MeSATP much greater than
ATP for
spasm.5. With raised tone, and in the presence of
indomethacin and alpha 8-SPT, desensitization to
alpha,beta-MeATP (100microM) completely and only slightly suppressed responses to
ATP and
2-MeSATP, respectively, as relaxants but had no effect on relaxant responses to
adenosine. The magnitude of the
spasms to
ATP and
2-MeSATP was considerably increased by desensitization with
alpha,beta-MeATP but the
spasm to KCl was not affected.6. With raised tone, and in the presence of
indomethacin and 8-SPT,
reactive blue 2 (10 AM) nonselectively antagonized
ATP, 2-MeATP, a,P-MeATP,
adenosine and
isoprenaline as relaxants.
Reactive blue 2 prevented the
spasms to
ATP and
2-MeSATP but not
spasm to KC1.7. With raised tone, and in the presence of
indomethacin,
suramin (100 microM) antagonized
ATP, but not
adenosine, as relaxants and antagonized
ATP, but not KC1, as spasmogens.8. It is proposed that
adenosine is susceptible to
nucleoside-specific uptake and acts predominantly via a P,-
purinoceptor and also by a non-PI-
purinoceptor mechanism.
ATP- and
alpha,beta-MeATP-induced relaxations probably occur via a P2x-purinoceptor. The anomalous nature of the 2-MeSATP-induced relaxation suggests it acts both via a P2x-purinoceptor and an additional mechanism. A P2y-purinoceptor is most likely to be involved in the
spasms to
ATP and
2-MeSATP. Therefore, the functional nature of the responses mediated by P2X- and P2y-purinoceptors, relaxation and
spasm respectively, are opposite to those seen in most smooth muscles.