Abstract:In several parts of the nervous system, adenosine has been shown to function as an extracellular neuromodulator binding to surface receptors on target cells. This study examines the possible role of adenosine in mediating light and circadian regulation of retinomotor movements in teleost cone photoreceptors. Teleost cones elongate in the dark and contract in the light. In continuous darkness, the cones continue to elongate and contract at subjective dusk and dawn in response to circadian signals. We report here that exogenous adenosine triggers elongation (the dark/ night movement) in isolated cone inner segment-cone outer segment preparations (CIS-COS) in vitro. Agonist/ antagonist potency profiles indicate that adenosine's effect on cone movement is mediated by an A2-like adenosine receptor, which like other A2 receptors enhances adenylate cyclase activity. Although closest to that expected for A2 receptors, the antagonist potency profile for CIS-COS does not correspond exactly to any known A2 receptor subtype, suggesting that the cone receptor may be a novel A2 subtype. Our findings are consistent with previous reports that retinal adenosine levels are higher in the dark, and further suggest that adenosine could act as a neuromodulatory "dark signal" influencing photoreceptor metabolism and function in the fish retina. Key Words: Adenosine-A2 receptors-Cone-Photoreceptor-Motility-Circadian. J. Neurochem. 72, 2345Neurochem. 72, -2355Neurochem. 72, (1999.In the teleost retina, photoreceptors elongate and contract in response to changes in light condition. Cones elongate in the dark and contract in the light; rods elongate in the light and contract in the dark (see Ali, 1975;Burnside and Nagle, 1983;Burnside and Dearry, 1986). These "retinomotor movements" serve to position the photopigment-bearing outer segments of the appropriate photoreceptors first in line for light absorption in either bright light conditions (cones first) or dim light conditions (rods first). Elongation and contraction take place in the neck-like myoid region between the photoreceptor's nucleus and outer segment. Cone motility is regulated not only by light, but also by circadian signals. Even when fish are maintained in constant darkness, their cones continue to elongate at subjective dusk and contract at subjective dawn (see Ali, 1975;Burnside and Ackland, 1984;Douglas et al., 1992).Cyclic AMP (cAMP) appears to play a critical role in the regulation of cone motility. Experimental treatments that elevate cAMP induce cones to elongate (i.e., elevating cAMP mimics the effect of darkness or subjective night) (Burnside et al., 1982;Burnside and Ackland, 1984;Dearry and Burnside, 1984). Exposing retinas or isolated cones to dopamine induces cones to contract even in constant darkness (i.e., dopamine mimics the effect of light or subjective day) (Dearry and Burnside, 1985;Pierce and Besharse, 1985;Dearry and Burnside, 1986b). Pharmacological studies of myoid contraction in isolated cone inner segment-cone outer segment preparations ...