Adenosine A1 receptors are not involved in contraction of canine gastric muscularis mucosae by adenosine analogues
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abstract
In vitro contractility studies were conducted in canine gastric muscularis mucosae muscle strips with the adenosine analogues 2-chloroadenosine (CIAD), 5'-N-ethylcarboxamidoadenosine (NECA), 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), S-PIA, N6-cyclohexyladenosine (CHA) and (2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine (CGS21680) as well as the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). Adenosine analogues contracted the muscle strips with the following rank order of potency: CPCA > NECA > CIAD > R-PIA > CHA > S-PIA > CGS21680. CPCA, R-PIA, and CHA were partial agonists. At a concentration selective for adenosine A1 receptors (50 nM), DPCPX did not alter the concentration-response curves to CIAD or CHA. However, at higher concentrations (1-10 microM), DPCPX antagonized CIAD-mediated contractions in a competitive manner (pA2 = 6.96; slope = 0.93). CIAD-mediated contraction was not altered by treatment of the muscle strips with tetrodotoxin (1 microgram/ml) or mepyramine (1 microM). Our results indicate that adenosine A1 receptors, nerves or mast cells are not involved in contraction of canine gastric muscularis mucosae by adenosine analogues.