Purine Antagonists in the Identification of Adenosine‐receptors in Guinea‐pig Trachea and the Role of Purines in Non‐adrenergic Inhibitory Neurotransmission

Section: Discussionsupporting

confidence: 93%

Dual effect of (−)‐N⁶‐phenylisopropyl adenosine on guinea‐pig trachea

Caparrotta¹,

Cillo²,

Fassina³

et al. 1984

“…The fact that ATP and adenosine are equipotent is in favour of a P2-type effect, whereas inhibition by theophylline would suggest a Pl-type effect. However, since we were unable to establish dose-response curves because of tachyphylaxis and of the relaxant effect of theophylline it is impossible to decide whether the inhibitory effect of theophylline was due to its specific spasmolytic activity or to antagonism at purinoceptor level, as has been noted in connection with its spasmolytic effect on the guinea-pig trachea (Coleman, 1980 …”

Section: Discussionmentioning

confidence: 92%

“…This effect is strongly potentiated by dipyridamole (Coleman & Levy, 1974), but whether Pi-or P2-purinoceptors (Bumstock, 1978), are involved, remains uncertain (Coleman, 1980;Clard, Small & Turnbull, 1980). In vivo, both ATP and adenosine may produce bronchoconstriction in guinea-pigs, and this has been correlated with effects on platelets (Lefort & Vargaftig, 1978).…”

Section: L2troductionmentioning

confidence: 99%

Contribution of Prostaglandins and Thromboxanes to the Adenosine and Atp‐induced Contraction of Guinea‐pig Isolated Trachea

Advenier

Bidet

Floch-Saint-Aubin

et al. 1982

In in vitro experiments adenosine 5′‐triphosphate (ATP) and adenosine were found to exert different effects on the guinea‐pig isolated trachea depending on whether the trachea had previously been contracted with acetylcholine (ACh) (6.6 × 10−6 m) or was at resting tone. ATP and adenosine (10−5 and 10−3 m) were equipotent in relaxing the precontracted guinea‐pig trachea, since concentrations of 1.09 ± 0.35 and 0.39 ± 0.16 mm respectively reduced by 25% the ACh‐induced contraction. ATP and adenosine (10−5 and 10−4 m) caused a moderate contraction of the guinea‐pig trachea under resting tone. This effect was antagonized by inhibitors of cyclo‐oxygenase (indomethacin 10−6m, aspirin 0.3 × 10−3m and 3 × 10−3m) and of thromboxane synthetase (nictindole 10−7m, imidazole 5 × 10−5 m), which suggests an indirect mechanism of action with release of arachidonic acid derivatives.

“…This latter observation probably represents inhibition of phosphodiesterase by theophylline (Amer & Kreighbaum, 1975) since responses to isoprenaline were also potentiated. It is known that phosphodiesterase inhibitors devoid of adenosine receptor antagonism potentiate responses to purines in this tissue (Coleman, 1980). 8-Phenyltheophylline is a more potent PI-antagonist than theophylline but has less effect on phosphodiesterase (Smellie, David, Daly & Wells, 1979).…”

Section: Resultsmentioning

confidence: 99%

EVIDENCE FOR AN A₂/R_a ADENOSINE RECEPTOR IN THE GUINEA‐PIG TRACHEA

Brown¹,

Collis²

1982

1 An attempt was made to determine whether the extracellular adenosine receptor that mediates relaxation in the guinea-pig trachea is of the Al/Ri or A2/Ra subtype.2 Dose-response curves to adenosine and a number of 5'-and N6-substituted analogues were constructed for the isolated guinea-pig trachea, contracted with carbachol. 3 The 5'-substituted analogues of adenosine were the most potent compounds tested, the order of potency being 5 '-N-cyclopropylcarboxamide adenosine (4 The difference in potency between the stereoisomers D-and L-PIA on the isolated trachea was at the most five fold. 5 Responses to low doses of adenosine and its analogues were attenuated after treatment with either theophylline or 8-phenyltheophylline. The responses to 2-chloroadenosine were affected to a lesser extent than were those to the other purines. 6 Adenosine transport inhibitors, dipyridamole and dilazep, potentiated responses to adenosine, did not affect those to NCPCA, NECA, L-PIA and D-PIA but significantly reduced the responses to high doses of 2-chloroadenosine.7 Relaxations evoked by 9-p-D-xylofuranosyladenosine which can activate intracellular but not extracellular adenosine receptors, were attenuated by dipyridamole but unaffected by 8-phenyltheophylline.8 The results support the existence of an extracellular A2/Ra subtype of adenosine receptor and an intracellular purine-sensitive site, both of which mediate relaxation.