ISSN:
1432-1912
Keywords:
PD 78,416
;
RS-74513-000
;
Mastoparan Acadesine
;
Guinea pig left atrium
;
Guinea pig ileum
;
Adenosine A1 receptors
;
CPA
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Previous reports on a series of benzoylthiophenes, including PD 81,723 {2-amino-4,5-dimethyl-3-(3-trifluoromethyl-benzoyl)thiophene}, have shown specific enhancement of agonist binding at the adenosine A1 receptor. We have studied the effects of two substituted benzoylthiophenes, PD 78,416 {thieno[2,3-c]pyridine-6(5H)-carboxylic acid, 2-amino-3-benzoyl-4,7-dihydro-ethyl ester} and RS-74513-000 {2-amino-4-ethyl-5-methyl-3-(3-trifluoro-methyl-benzoyl) thiophene} on response elicited by adenosine A1 receptors in isolated guinea pig left atrium and ileum. In the electrically paced left atrium, PD 78,416 antagonized negative inotropic effect elicited by the agonist CPA {N6-cyclopentyladenosine} with a pKB value of 6.2 ± 0.2 (n = 4) . At a low concentration which had no antagonistic effect (0.1 μM), PD 78,416 enhanced the effect of CPA. The concentration-response curve to CPA was shifted leftward by 5.1 fold (95% confidence limits 2.4–11.2). In field stimulated isolated ileum, PD 78,416 (0.1, 0.3, 1 μM) did not enhance or antagonize effects of CPA. At concentrations above 1 μM, PD 78,416 decreased electrically induced contraction. This effect was not sensitive to adenosine deaminase and was not antagonized by the A1 antagonist CPX {8-cyclopentyl-1,3-dipropyl-xanthine} (1 μM). Unlike PD 78,416, RS-74513-000 (0.01, 0.1, 1, 3, 10 μM) did not antagonize or enhance effects of CPA in the left atrium. However, effects of CPA in ileum were enhanced by RS-74513-000 (1 and 3 μM). Maximum enhancement was observed at 3 μM; the concentration-response curve to CPA was shifted leftward by 3.2 fold (95% confidence limits 2.4–4.2). Higher concentrations of RS-74513-000 (10 and 30 μM) decreased electrically induced contraction, this effect was not reversed by CPX. These findings confirmed that functional effects of A1 adenosine receptor may be enhanced by substituted benzoylthiophenes in vitro. The differential effect of PD 78,416 and RS-74513-000 on cardiac and ileal A1 receptors suggests that it may be possible to design selective enhancers for cardiac and neural functions.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00176776
Permalink
