Dopamine and plasticity of horizontal cell function in the teleost retina: Regulation of a spectral mechanism through D1-receptors

In 1979, two categories of dopamine (DA) receptors (designated as D-1 and D-2) were identified on the basis of the ability of a limited number of agonists and antagonists to discriminate between these two entities. In the past 5 years agonists and antagonists selective for each category of receptor have been identified. Using these selective drugs it has been possible to attribute the effects of DA upon physiological and biochemical processes to the stimulation of either a D-1 or a D-2 receptor. Thus, DA-induced enhancement of both hormone release from bovine parathyroid gland and firing of neurosecretory cells in the CNS of Lymnaea stagnalis has been attributed to stimulation of a D-1 receptor. Likewise, the DA-induced inhibition of the release of prolactin and alpha-MSH from the pituitary gland, as well as of acetylcholine, DA and beta-endorphin from brain, the DA-induced inhibition of chemo-sensory discharge in rabbit carotid body and the DA-induced hyperpolarization of neurosecretory cells in the CNS of Lymnaea stagnalis have been attributed to stimulation of a D-2 receptor. Independently two categories of DA receptors (designated as DA-1 and DA-2) were identified in the cardiovascular system. Stimulation of a DA-1 receptor increases the vascular cyclic AMP content and causes a relaxation of vascular smooth muscle in renal blood vessels, whereas stimulation of a DA-2 receptor inhibits the release of norepinephrine from certain postganglionic sympathetic neurons. Recent studies with the newly developed drugs discriminating between D-1 and D-2 receptors suggest however that the independently developed schemata for classification of dopamine receptors in either the central nervous and endocrine systems or the cardiovascular system are similar although maybe not completely identical.

In the teleost retina, cone horizontal cells receive extensive innervation from dopaminergic interplexiform cells, and possess dopamine receptors whose activation stimulates adenylate cyclase. Exogenously applied dopamine modifies several aspects of horizontal cell activity in the intact retina, including the responsiveness of these neurons to light and the strength of electrical coupling between them. We have used whole-cell voltage clamp methods to examine whether dopamine can alter the light-responsiveness of horizontal cells by changing their sensitivity to the neurotransmitter released by the photoreceptors. We report that dopamine and cyclic AMP, although having little direct effect on resting membrane conductance, greatly enhance ionic conductances gated by kainate, an agonist of the transmitter released by the photoreceptors, and by L-glutamate, the agent proposed to be the photoreceptor transmitter. Our results provide the first direct evidence for dopaminergic regulation of excitatory amino-acid neurotransmission in the vertebrate nervous system and suggest a possible mechanism to explain the reduction in the responsiveness of horizontal cells observed when retinas are treated with dopamine.