Purine receptors and guinea-pig trachea: evidence for a direct action of ATP.
1. Adenosine (3-300 microM) and ATP (1-300 microM) each induced concentration-dependent relaxation of guinea-pig isolated tracheal preparations that had been precontracted with methacholine. 2. Ectonucleotidase enzymes on the trachea dephosphorylated ATP to form adenosine which was then further metabolised to inosine and hypoxanthine. 3. Dipyridamole (2 microM) inhibited the metabolism of adenosine but did not inhibit the dephosphorylation of ATP. Nevertheless dipyridamole potentiated the effects of both adenosine and ATP in relaxing tracheal smooth muscle. 4. Although adenosine 5'-[beta,gamma-imido] triphosphate (AMP-PNP), an analogue of ATP, was resistant to catabolism by ectonucleotidases, it was more potent at inducing relaxation than either ATP or adenosine, and was also potentiated by dipyridamole (2 microM). 5. Relaxations induced by ATP and by AMP-PNP were more rapid than those induced by adenosine. 6. We therefore conclude that the intact ATP molecule can itself induce relaxation of the guinea-pig trachea, without first having to be metabolised to adenosine, and furthermore that dipyridamole does not act simply by inhibiting the degradation (or uptake) of adenosine.
Welford
L A
LA
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Anderson
W H
WH
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D004176:Dipyridamole / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects*
D008688:Methacholine Compounds; D011983:Receptors, Purinergic; D000266:Adenylyl Imidodiphosphate; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D000241:Adenosine