Purine Receptors in the Trachea: Is There a Receptor for Atp?

1 The effects of adenosine, adenosine triphosphate (ATP) and structural analogues have been studied on glucagon secretion from the isolated perfused pancreas of the rat in the presence of glucose (2.8 mM). 2 Adenosine induced a transient increase of glucagon secretion. This effect was concentrationdependent in the range of 0.165 to 165 jiM. ATP also induced an increase, but the effect was no greater at 165 jiM than at 16.5 jiM. 3 2-Chloroadenosine, an analogue more resistant to metabolism or uptake systems than adenosine, was more effective. Among the three structural analogues of ATP or ADP studied, 13,y-methylene ATP which can be hydrolyzed into AMP and adenosine had an effect similar to adenosine or ATP at the same concentrations (1.65 and 16.5 tLM); in contrast a, P-methylene ATP and a, 3-methylene ADP (resistant to hydrolysis into AMP and adenosine) were ineffective. 4 Theophylline (50 jiM) a specific blocker of the adenosine receptor, suppressed the glucagon peak induced by adenosine, 2-chloroadenosine, ATP and f, y-methylene ATP (1.65 jM). 6 These results support the hypothesis of adenosine receptors (Pl-purinoceptors) on the pancreatic glucagon secretory cells and indicate that ATP acts after hydrolysis to adenosine.

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 92%

Effects of adenosine, adenosine triphosphate and structural analogues on glucagon secretion from the perfused pancreas of rat in vitro

Chapal¹,

Loubatières-Mariani²,

Roye³

et al. 1984

“…Adenosine 5'-triphosphate (ATP) and adenosine have been shown to exert a relaxant effect on a variety of guinea-pig isolated lung preparations (Coleman & Levy, 1974;Coleman, 1976;Farmer & Farrar, 1976;Christie & Satchell, 1980). 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).…”

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.

“…Purine nucleosides are potent relaxants of tracheal musculature (Coleman, 1976;Farmer & Farrar, 1976) and according to the classification of Burnstock (1978) appear to mediate their effects through an extracellular adenosine (Pl) receptor (Farmer & Farrar, 1976; Christie & Satchell, 1980). A subclassification of adenosine receptors has been proposed by two independent groups based on their observations of the adenylate cyclase system.…”

Section: Introductionmentioning

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.