The relationship between variations in levels of serotonin acetyltransferase activity and cGMP content in cultured chick pineal glands
Chick pineal glands cultured in continuous darkness exhibited a circadian rhythm in 3′,5′-cyclic GMP (cGMP) content. cGMP content increased earlier and fell later than in glands incubated under diurnal lighting. A "spike" of further increase in cGMP content preceded start of decline in acetyl-CoA:arylamine N-acetyltransferase (NAT) activity.Theophylline or 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (compound Ro 20.1724) alone markedly stimulated increase of NAT activity in the dark, and retarded subsequent loss of activity either in the dark or in the photoperiod of a diurnal cycle of illumination. In constant darkness a combination of the two agents elicited greater increases of NAT than either alone and suppressed subsequent loss of activity for several hours. Under diurnal lighting conditions the combination was only slightly more effective than either alone. Compound Ro 20.1724 suppressed the precipitous loss of NAT activity seen when glands are transferred prematurely to the light. However, neither the rate or extent of loss of activity was greatly affected by theophylline.Effects of theophylline and compound Ro 20.1724 upon levels of NAT activity appeared to be due primarily to effects upon the process(es) by which enzyme activity is lost. They could not be attributed solely to effects upon pineal contents of cGMP and (or) 3',5'-cyclic AMP (cAMP). Theophylline alone was as effective as the drug combination in eliciting and maintaining elevated pineal content of cGMP, but had little effect upon cAMP content. Compound Ro 20.1724 alone elicited large increases in pineal contents of both nucleotides but did not sustain them.