Though there is considerable evidence that dopamine is an important retinal neuromodulator that mediates many of the changes in the properties of retinal neurons that are normally seen during light adaptation, the mechanism by which dopamine release is controlled remains poorly understood. In this paper, we present evidence which indicates that dopamine release in the retina of the tiger salamander, Ambystoma tigrinum, is driven excitatorily by a cholinergic input. We compared the effects of applying carbachol to those of dopamine application on the responses of rods, horizontal cells, and bipolar cells recorded intracellularly from the isolated, perfused retina of the tiger salamander. Micromolar concentrations of dopamine reduced the amplitudes of rod responses throughout the rods' operating range. The ratio of amplitudes of the cone-driven to rod-driven components of the responses of both horizontal and bipolar cells was increased by activation of both D1 and D2 dopamine receptors. Dopamine acted to uncouple horizontal cells and also off-center bipolar cells, the mechanism in the case of horizontal cells depending only upon activation of D1 receptors. Carbachol, a specific cholinomimetic, applied in five- to ten-fold higher concentrations, produced effects that were essentially identical to those of dopamine. These effects of carbachol were blocked by application of specific dopamine blockers, however, indicating that they are mediated secondarily by dopamine. We propose that the dopamine-releasing amacrine cells in the salamander are under the control of cells, probably amacrine cells, which secrete acetylcholine as their transmitter.

The contractile response of smooth muscles to spasmogens can be divided into two components by modifying the extracellular Ca2+ concentration. The phasic component depends on the mobilization of Ca2+ from intracellular stores whereas the tonic component depends, to a large extent, on the influx of extracellular Ca2+. The present study was designed to investigate the effect of ketamine on the tonic response to carbachol or histamine in the guinea pig trachea. Tracheal spirals from female guinea pigs were mounted in organ baths filled with aerated physiological buffer, and their isometric tension was measured. The phasic response to 10−7m carbachol or 10−5m histamine in Ca2+ -free, ethylene glycol-bis(β-aminoethyl ether)-N, N,N',N'-tetraacetic acid-containing buffer and the tonic response to each spasmogen after restoring [Ca2+] in the buffer was measured in the absence or presence of ketamine. In the presence of normal physiological buffer, ketamine decreased the contractions induced by carbachol or histamine in a dose-dependent fashion. No measurable phasic response to either carbachol or histamine was obtained in our preparation. Ketamine (5 × 10−5m−10−3m) reduced the tonic response to 10−7m carbachol to 79.5±2.7−4.3±0.7% of the response without ketamine. Similarly, ketamine (5 × 10−4m−2 × 10−3m) decreased the tonic response to 10−5m histamine to 80.7±3.9−23.0±3.2% of the response in the absence of ketamine. Our findings support the hypothesis that ketamine inhibits the paracrine agent-induced contractions of smooth muscles by interfering with the influx of extracellular Ca2+ or with an intracellular event(s) requiring extracellular Ca2+.