The circadian rhythm of guanylate cyclase and its interrelationship to rat liver chalone.

Guanylate cyclase [E.C.4.6.1.2], the enzyme that catalyzes the production of cyclic GMP, was found to have a circadian rhythm in chick embryo livers with peak levels of basal activity at 9 p.m. and with another peak of activity at 6 a.m. The lowest levels of basal activity were at 3 a.m. and 3 p.m. Liver contains an inhibitor of cellular mitosis, i.e., chalone, which has its maximal inhibitory effect on mitosis when isolated at 9 p.m. Utilizing this 9 p.m. liver chalone in vivo reinforced the endogenous rhythm of guanylate cyclase but reset it at a higher level 4 hours after injection. This maximally effective hepatic chalone inhibited guanylate cyclase activity in vitro approximately 50 percent in rat liver, kidney, small intestine, heart and pancreas.