Variations in cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate content and efflux from the photosensitive pineal organ of the pike in culture.

The photoreceptor cells of the pike pineal organ transduce 24-h light/dark (LD) information to synchronize the clocks driving the melatonin (MEL) rhythm. In fish, the nocturnal rise in MEL synthesis is associated with an increase in cyclic adenosine 3', 5'-monophosphate (cAMP) production and with Ca2+ entry, through voltage-gated channels. Light induces inhibition of MEL synthesis and a depression of cAMP content, as well as closure of Ca2+ channels. Cyclic guanosine 3',5'-monophosphate (GMP) levels also are reduced upon acute illumination but this second messenger of phototransduction does not appear to be directly involved in the control of MEL metabolism. It is not known whether cAMP and/or cGMP are components of the clock machinery. In this study we measured cAMP and cGMP contents (static culture) and release (perifusion culture) using pike pineal organs maintained under LD or DD (constant darkness). Under LD, cAMP levels were low at noon and midnight, and high at dawn and dusk, in organs as well as in perfusates. This pattern was maintained under DD, with a major peak occurring at the beginning of subjective light, and a minor peak at the beginning of subjective darkness; only one peak during the subjective light was seen in the perfusates. Under DD, the MEL rhythm displays only one peak during the subjective night. It is suggested that increases in cAMP might not always be correlated with increases in MEL secretion. Under LD, variations in cGMP content were not statistically significant; however, in the perfusates, the levels were higher during the night than during the day. This suggests that: (1) extrusion participates in the regulation of intracellular levels of cGMP, (2) nocturnal synthesis of cGMP is higher than its catabolism, and (3) synthesis is increased during the day to compensate for the light-induced activation of catabolism. Under DD, the cGMP content and release were higher during the subjective night than during the subjective day, revealing a circadian component in the regulation of cGMP metabolism. This may provide the basis for the generation of membrane-related circadian events including variations in membrane potential, in the opening/closure of voltage-gated channels (e.g. Ca2+ channels), or in enzyme activities (adenylyl cyclase, cGMP-dependent phosphodiesterase).