SYNERGISTIC INCREASE IN CA2-TOXIN-SENSITIVE PATHWAY IN EPITHELIAL-CELLS OF THE RABBIT CILIARY BODY( PRODUCED BY A(1) ADENOSINE AND MUSCARINIC RECEPTOR ACTIVATION VIA A PERTUSSIS)

The combined effects of adenosine and acetylcholine on the intracellul ar free-Ca2+ concentration in nonpigmented epithelial cells of the rab bit ciliary body were investigated using fura-2 fluorescence-ratio ima ging. 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-cyclopentyladenosin e 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)-s pecific antagonist 8-cyclopentyl-1,3-dipropylxanthine. However, the A( 2)-specific agonist l)-phenethylamino]-5'-N-ethylcarboxamide-adenosine and the antagonist 3,7-dimethyl-1-(2-propynyl)xanthine were without e ffect. Incubation of the tissue with pertussis toxin did not alter the response to ACh alone but eliminated the synergistic effect of adenos ine (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 a ppears to occur via a pertussis-toxin-sensitive pathway, perhaps throu gh G(i). (C) 1997 Academic Press Limited.