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 syn chronize the clocks driving the melatonin (MEL) rhythm. In fish, the nocturnal rise in MEL synthesis is associa ted with an increase in cyclic adenosine 3',5'-monophosphate (cAMP) pr oduction and with Ca2+ entry, through voltage-gated channels. Light in duces inhibition of MEL synthesis and a depression of cAMP content, as well as closure of Ca2+ channels. Cyclic guanosine 3',5'-monophosphat e (GMP) levels also are reduced upon acute illumination but this secon d messenger of phototransduction does not appear to be directly involv ed 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 measur ed cAMP and cGMP contents (static culture) and release (perifusion cul ture) using pike pineal organs maintained under LD or DD (constant dar kness). 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 dark ness; only one peak during the subjective Light was seen in the perfus ates. Under DD, the MEL rhythm displays only one peak during the subje ctive night. It is suggested that increases in cAMP might not always b e correlated with increases in MEL secretion. Under LD, variations in cGMP content were not statistically significant, however, in the perfu sates, the levels were higher during the night than during the day. Th is suggests that: (1) extrusion participates in the regulation of intr acellular levels of cGMP, (2) nocturnal synthesis of cGMP is higher th an its catabolism, and (3) synthesis is increased during the day to co mpensate 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 reg ulation of cGMP metabolism. This may provide the basis for the generat ion of membrane-related circadian events including variations in membr ane potential, in the opening/closure of voltage-gated channels (e.g. Ca2+ channels), or in enzyme activities (adenylyl cyclase, cGMP-depend ent phosphodiesterase).