Synergistic increase in Ca2+ produced by A(1) adenosine and muscarinic receptor activation via a pertussis-toxin-sensitive pathway in epithelial cells of the rabbit ciliary body

The combined effects of adenosine and acetylcholine on the intracellular free-Ca2+ concentration in nonpigmented epithelial cells of the rabbit ciliary body were investigated using fura-2 fluorescence-ratio imaging. Acetylcholine (10 mu M) by itself produced a modest increase in [Ca2+](i). Acetylcholine in combination with adenosine, or with the A(1)-specific agonists N-6-cyclohexyl-adenosine, N-6-cyclopentyladenosine and (R)-N-6-(2-phenyl-1-methylethyl)-adenosine (0.1-1 mu M), induced a massive increase in [Ca2+](i), which could be blocked by the A(1)-specific antagonist 8-cyclopentyl-1,3-dipropylxanthine. However, the A(2)-specific agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamide-adenosine and the antagonist 3,7-dimethyl-1-(2-propynyl)xanthine were without effect. Incubation of the tissue with pertussis toxin did not alter the response to ACh alone but eliminated the synergistic effect of adenosine (or of epinephrine), It was concluded that in the epithelial cells of the rabbit ciliary body, adenosine and epinephrine synergistically potentiate the rise in [Ca2+](i) produced by ACh. This potentiation appears to occur via a pertussis-toxin-sensitive pathway, perhaps through G(i). (C) 1997 Academic Press Limited.