CHARACTERIZATION OF ADENOSINE RECEPTORS ON RAT ILEUM, ILEAL LONGITUDINAL MUSCLE AND MUSCULARIS MUCOSAE

Adenosine receptors were studied in isolated rat ileum, ileal longitud inal muscle and muscularis mucosae, using a range of agonists and an a ntagonist. In the rat ileal longitudinal muscle adenosine receptor ago nists relaxed the tissues. N-6-cyclopentyladenosine (CPA) was more pot ent than 5'-N-ethylcarboxamidoadenosine (NECA) or adenosine and 1,3-di propyl-8-cyclopentylxanthine (DPCPX) (1 nM) gave a 5-fold parallel shi ft to the right of the concentration-response curves to both CPA and N ECA corresponding to an apparent pA(2) value of 9.6 suggesting that th e agonists relax via adenosine A(1) receptors. In the intact ileum ade nosine receptor agonists also relaxed the tissue but NECA and CPA were equipotent. DPCPX (3 nM) however inhibited responses to both CPA and NECA with dose-ratios of 8 and 15.6, corresponding to pA(2) values of 9.3 and 9.7, respectively. DPCPX (300 nM) gave a much greater shift to the right of the concentration-response curve to NECA with a dose-rat io of 769, corresponding to an apparent pA(2) of 9.4. This suggests th at the agonists are acting at adenosine A(1) receptors to cause relaxa tion of the whole tissue. Adenosine receptor agonists contracted rat i leal muscularis mucosae with a potency order indicative of an A(1) ade nosine receptor. DPCPX (3-100 nM) antagonized responses to CPA giving a linear Schild plot with a slope close to unity and a pA(2) of 8.4 su ggesting an action on adenosine A(1) receptors. (C) 1997 Elsevier Scie nce B.V.