Influence of diurnal cycles on biochemical parameters of drug sensitivity: the pineal gland as a model

Diurnal cycles in physical parameters in the environment modulate biochemical and physiological circadian rhythms in experimental animals, including cycles in the sensitivity to external influences. Environmental lighting synchronizes cycles of indole metabolism and melatonin synthesis in the rat pineal gland by modulating the activity of postganglionic sympathetic nerves. As a consequence, the sensitivity of pineal N-acetyltransferase to stimulation by isoproterenol or by dibutyryl cyclic AMP varies diurnally. Also, the capacity of actinomycin D to inhibit this induction varies with circadian periodicity. The cycles in sensitivity to isoproterenol reflect cycles in the system that regulates cyclic AMP production, and include variation in the availability of specific B-adrenergic binding sites, and in the sensitivity of receptor-coupled adenylate cyclase to catecholamines. Further, a variation in the response to dibutyryl cyclic AMP indicates in addition the participation of intracellular controls in the regulation of the sensitivity of N-acetyltransferase to catecholamines. The varying sensitivity to actinomycin D suggests a changing requirement for the synthesis of RNA as a function of prior environmental lighting conditions. The basic nature of these sensitivity changes suggests that diurnal cycles of environmental lighting may similarly affect other systems.