title: Enhancement of adenosine A1 receptor functions by benzoylthiophenes in guinea pig tissues in vitro.
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 microM), 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 microM) did not enhance or antagonize effects of CPA. At concentrations above 1 microM, 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 microM). Unlike PD 78,416, RS-74513-000 (0.01, 0.1, 1, 3, 10 microM) 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 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010455:Peptides; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011725:Pyridines / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D012263:Ribonucleosides / Q000494:pharmacology; D058924:Thienopyridines; D013876:Thiophenes / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology
chemical_list: D058892:Adenosine Deaminase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011725:Pyridines; C096826:RS 74513-000; D018047:Receptors, Purinergic P1; D012263:Ribonucleosides; D058924:Thienopyridines; D013876:Thiophenes; D014862:Wasp Venoms; C096825:ethyl 2-amino-3-benzoyl-4,7-dihydrothieno(2,3-c)pyridine-6(5H)-carboxylate; C075004:PD 81723; D000620:Aminoimidazole Carboxamide; C048599:N(6)-cyclopentyladenosine; C011651:acadesine; C037500:mastoparan; D000241:Adenosine