Adenosine A1 and A(2b) receptors coupled to distinct interactive signaling pathways in intestinal muscle cells

K. S. Murthy, L. McHenry, J. R. Grider, G. M. Makhlouf

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

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 A(2a) agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N- ethylcarboxamido adenosine, was a very weak relaxant agent, and the selective A(2a) 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. The results indicate that both A1 and A2 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 pathways: Ca2+ mobilization and inhibition of cAMP via A1 receptors, and stimulation of cAMP via A(2b) receptors.

Original languageEnglish (US)
Pages (from-to)300-306
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume274
Issue number1
StatePublished - 1995

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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