Adenosine A1 and A2b receptors coupled to distinct interactive signaling pathways in intestinal muscle cells.
Adenosine receptors and the signaling pathways to which they are coupled were examined in dispersed intestinal muscle cells. The receptors were characterized by their ability to induce contraction or relaxation, 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 and cAMP; the contraction was mimicked by the A1 selective agonist, cyclopentyladenosine. A selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine, and pertussis toxin abolished contraction and the increase in [Ca2+]i and augmented the increase in cAMP. Conversely, a preferential A2 antagonist, 9-chloro-2-(2-furyl) [1,2,4]triazolo[1,5-c]quinazolin-5-amine augmented contraction and the increase in [Ca2+]i and abolished the increase in cAMP; a cAMP-kinase inhibitor, Rp-cAMP[S], had a similar effect, augmenting contraction and the increase in [Ca2+]i. Adenosine elicited also relaxation of maximally contracted cells that increased or decreased in parallel with cAMP. The selective A2a agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine, was a very weak relaxant agent, and the selective A2a antagonist, 8-(3-chlorostyryl)caffeine, had no effect on adenosine-induced relaxation. In cells where only A1 receptors were preserved, the cAMP response to adenosine was abolished, although contraction and [Ca2+]i were increased to the same extent as when naive cells were treated with the A2 antagonist. Conversely, in cells where only A2 receptors were preserved, contraction and the increase in [Ca2+]i were abolished and the increase in cAMP was augmented to the same level as when naive cells were treated with the A1 antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Murthy
K S
KS
Department of Medicine, Medical College of Virginia, Richmond, USA.
McHenry
L
L
Grider
J R
JR
Makhlouf
G M
GM
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction
D018047:Receptors, Purinergic P1; D000241:Adenosine