Various drugs known or expected to increase the levels of cyclic nucleotides in cells were applied to isolated superfused frog retinae, and their influence on the aspartate-isolated a-wave was studied. Isobutylmethylxanthine (IBMX), triacetylguanosine (TAG), and dimethylaminopurine (DAMP) strongly influenced the responses elicited from dark-adapted retinae by flashes of light: With all three drugs the response amplitude was increased, and latency and time to peak were prolonged. If, on the other hand, the retinae were light-adapted by background light of various intensities, the drugs showed different effects on the response amplitude: IBMX either did not influence the amplitude at all or even caused a decrease (4 of 6 experiments), DAMP decreased the amplitude and TAG caused an increase of the amplitude in 2 of 3 experiments. But latency and time to peak were still prolonged by all three drugs. When dark-adapted retinae were superfused with IBMX or TAG Ringer solution and simultaneously calcium concentration was raised, different effects of calcium on the three measured parameters of the a-wave were observed: By increasing the extracellular calcium concentration the increase of the amplitude caused by drugs was reversed, down or even below the control level, whereas latency and time to peak remained prolonged. Thus, both an increased calcium level and light adaptation had the same effect, namely to reverse only that part of the drug effect concerning the amplitude but not latency or time to peak of the response. The data suggest that calcium and cyclic nucleotides act through different ways in the rod cells.
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