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Contractile effect of α,β ‐methylene ATP on the guinea‐pig isolated trachea
Author(s) -
Candenas ML,
Devillier P.,
Naline E.,
Advenier C.
Publication year - 1992
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1992.tb00104.x
Subject(s) - purinergic receptor , adenosine , methylene , chemistry , methylene blue , theophylline , guinea pig , contraction (grammar) , medicine , adenosine receptor , endocrinology , pharmacology , stereochemistry , receptor , medicinal chemistry , biochemistry , agonist , photocatalysis , catalysis
Summary— The effects of α,β ‐methylene adenosine 5′‐triphosphate ( α,β ‐methylene ATP), 2‐chloroadenosine and R‐PIA (N 6 ‐(L‐2‐phenylisopropyl)‐adenosine) and their interaction with dipyridamole, indomethacin, 8‐phenyl‐theophylline, diazepam and other agonists of central or peripheral benzodiazepine receptors were studied on the guinea‐pig isolated trachea. α,β ‐methylene ATP exerted contractile effects on the guinea‐pig isolated trachea; ‐ log EC 50 and E max values were 8.86 ± 0.19 and 31.3 ± 2.3 ( n = 31) (% vs acetylcholine 10 −3 M) respectively. In comparison with other purinergic receptor agonists, the rank order of potency was: α,β ‐methylene ATP > 2‐chloroadenosine > R‐PIA. α,β ‐methylene ATP and 2‐chloroadenosine had significantly ( P < 0.05) greater efficacy ( E max ) than R‐PIA. Indomethacin (3 times 10 −6 M) and 8‐phenyltheophylline (10 −7 to 10 −5 M) significantly reduced the contractile effect of 2‐chloroadenosine and R‐PIA but did not affect α,β ‐methylene ATP‐induced contraction. Conversely, dipyridamole significantly reduced (10 −7 M) or suppressed (10 −6 M) the contractile effects of α,β ‐methylene ATP whereas it only partially reduced (10 −6 M) the contractile effects of high concentrations of 2‐chloroadenosine or R‐PIA. Diazepam potentiated the efficacy of α,β ‐methylene ATP. The E max (% vs acetylcholine 10 −3 M) values were 26.1 ± 2.0 ( n = 10) in control conditions and 45.9 ± 4.6 ( n = 5; P < 0.05) in the presence of diazepam 10 −5 M. Diazepam did not modify the contractile effects of 2‐chloroadenosine or R‐PIA. Ro5–4864 (10 −7 to 10 −5 M), an agonist of peripheral benzodiazepine receptors, potentiated the contractile effects of α,β ‐methylene ATP to the same extent as diazepam. Clonazepam, an agonist of central benzodiazepine receptors, did not modify these effects. Antagonists of central (flumazenil) or peripheral (RP 52028) benzodiazepine receptors had no influence on the interaction between diazepam or Ro5–4864 and α,β ‐methylene ATP. In conclusion, α,β ‐methylene ATP exerts on guinea‐pig isolated trachea a contractile effect which is not modified by indomethacin and 8‐phenyltheophylline, but is reduced by dipyridamole. It is suggested that this effect might involve P 2x receptor stimulation.