ADENOSINE A(1) AND A(2B) RECEPTORS COUPLED TO DISTINCT INTERACTIVE SIGNALING PATHWAYS IN INTESTINAL MUSCLE-CELLS

Adenosine receptors acid the signaling pathways to which they are coup led were examined in dispersed intestinal muscle cells. The receptors were characterized by their ability to induce contraction or relaxatio n, mobilize Ca2+ and stimulate or inhibit cAMP, in naive cells and in cells where only one receptor type was preserved by selective receptor protection. Adenosine elicited contraction and increased [Ca2+](i) an d cAMP; the contraction was mimicked by the A(1) selective agonist, cy clopen-tyladenosine. A selective A(1) antagonist, 8-cyclopentyl-1,3-di propylxanthine, and pertussis toxin abolished contraction and the incr ease in [Ca2+](i) and augmented the increase in cAMP. Conversely, a pr eferential A, antagonist, -(2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5 -amine augmented contraction and the increase in [Ca2+](i) acid abolis hed the increase in cAMP; a cAMP-kinase inhibitor, Rp-cAMP[S], had a s imilar effect, augmenting contraction and the increase in [Ca2+](i). A denosine elicited also relaxation of maximally contracted cells that i ncreased or decreased in parallel with cAMP. The selective A(2a) agoni st, -carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine, was a very weak relaxant agent, and the selective A(2a) antagonist, 8-(3-c hlorostyryl)caffeine, had no effect on adenosine-induced relaxation. I n cells where only A(1) receptors were preserved, the cAMP response to adenosine was abolished, although contraction and [Ca2+](i) were incr eased to the same extent as when naive cells were treated with the A(2 ) antagonist. Conversely, in cells where only A(2) receptors were pres erved, contraction and the increase in [Ca2+](i) were abolished and th e increase in cAMP was augmented to the same level as when naive cells were treated with the A(1) antagonist. The results indicate that both A(1) and A(2) receptors are present on intestinal longitudinal muscle cells coupled to distinct but interactive signaling pathways. The net response to adenosine reflects concurrent activation of three pathway s: Ca2+ mobilization and inhibition of cAMP via A(1) receptors, and st imulation of cAMP via A(2b) receptors.