Chronopharmacology of isoprenaline: the effects on rat plasma concentrations of large neutral amino acids depend on time of day for administration.

This investigation was undertaken in order to test our hypothesis, that the endogenous circadian rhythms in large neutral amino acids (LNAAs) in plasma are partly regulated by beta-adrenergic mechanisms. The beta-adrenoceptor agonist isoprenaline, which is known to decrease the concentrations of rat plasma LNAAs, was given at several time-points over a full 24-h period intraperitoneally to rats, which were killed 1 h later. Isoprenaline, administered in the evening, decreased the plasma amino acid concentrations more than it did in the same doses given in the morning. Also the potency of isoprenaline was in this respect higher in the evening than in the morning. This finding, of a time-of-day dependent relationship between the effects of a beta-adrenoceptor agonist and plasma LNAA concentrations, supports our hypothesis, that beta-adrenergic mechanisms are involved in the endogenous regulation of the plasma LNAA rhythms. We suggest that the known endogenous circadian variation in sympathetic activity, which gives rise to a reciprocal rhythm in beta-adrenoceptor responsiveness, could be one factor explaining that part of the circadian rhythm in plasma LNAA concentrations, which is not due to variations in food intake.